The Sminthophile

Off topic

2009-03-13T11:29:00.000-07:00

No mice here. Just great music.

What do you think?

2009-03-05T06:03:00.000-08:00

OK, I've been busy and will continue to be busy for a few weeks. In the meantime, I present this for your perusal. You know that myth about elephants being afraid of mice?

Mouse v elephant
Uploaded by krupis

Anyone care to critique the scientific method in this experiment?

The evolution of evolution

2009-02-17T07:03:00.000-08:00

OK, so I'm a little behind the times. I wanted to wish Charles Darwin a happy birthday last week, but life got in the way. While we extol the virtues of Darwin and his theory of evolution, I want to talk a little bit about another theory of evolution, that of Jean-Baptiste Lamarck.

The Lamarckian theory of evolution states that acquired traits can be inherited. The classic example is the long neck of the giraffe. Lamarck's explanation would be that as giraffes stretch up to eat the leaves of trees, their necks become longer and stronger. Their offspring would then have long necks. The Darwinian explanation would be that those giraffes with genetically determined longer necks would be better able to reach the leaves up in the trees, and thus better able to survive and produce offspring, passing along their long-neck genes to their young.

The more recent field of epigenetics is lending some credence to Lamarck's ideas. Recently published papers in Biological Psychiatry and The Journal of Neuroscience show that experience can alter certain traits in mice and that these traits can be inherited.

More here.

I'm not saying that Darwin was wrong, or that giraffes owe their necks to stretching instead of genes. Like any scientific theory, Darwin's theory of evolution has evolved and will continue to evolve as new information is obtained. It doesn't invalidate the theory. It just makes it more elegant.

How the other half blogs

2009-01-16T06:00:00.000-08:00

If you want to find out about my other ~~life~~ blog, go here.

Fat-bottomed mice

2009-01-05T17:49:00.000-08:00

From telegraph.co.uk

Having a large bottom could help protect against diabetes, claims study
Having a large behind and hips may actually have health benefits and protect against diabetes, according to a new study.

By Richard Alleyne, Science Correspondent
Last Updated: 3:57PM GMT 02 Jan 2009

Researchers believe the type of fat that accumulates around the hips and buttocks, rather than around your stomach, may offer some protection against developing the disease.

But fat that collects around the stomach, known as visceral fat and often resulting in a 'beer belly', can raise a person's risk of diabetes and heart disease.

That means people with pear-shaped bodies, with fat deposits in the buttocks and hips, are likely to be less prone to these disorders, concluded the research at Harvard Medical School.

Scientists believe that the more beneficial fat, called subcutaneous fat because it collects just under the skin, may help to improve sensitivity to the hormone insulin, which regulates blood sugar levels.

Dr Ronald Kahn, who led the research published in Cell Metabolism, said obesity in subcutaneous areas - the 'pear' shape - might decrease risks.

He carried out experiments by artificially switching the two types of fat around the body of mice and seeing what effect it had.

"The surprising thing was that it wasn't where the fat was located, it was the kind of fat that was the most important variable," he said:

"Even more surprising, it wasn't that abdominal fat was exerting negative effects, but that subcutaneous fat was producing a good effect.

"Animals with more subcutaneous fat didn't gain as much weight as they got older, had better insulin sensitivity, lower insulin levels and were improved all around."

Mice given subcutaneous fat transplanted into their bellies started to slim down after several weeks.

They also showed improved blood sugar and insulin levels compared to other mice.

Dr Kahn said this is an important result because it shows that not all fat is bad and could help prevent the onset of type 2 diabetes.

The team are trying to find the substances produced in subcutaneous fat that provide the benefit as this could lead to the development of new drugs which mimic this effect.

There are more than 2.5 million people in Britain with diabetes and it is estimated another half a million have the condition but do not know it.

Funny, I couldn't find the citation for a "new study," just this one.

Mousy Mittens

2008-12-24T07:15:00.000-08:00

For ~~both~~ all of my loyal readers...

A gift, handmade by Ms. Ether.

Keep those paws warm!!

Revenge of the Rodents

2008-12-20T17:32:00.000-08:00

From arkansasmatters.com:

Mice Start Deadly Fire That Kills 100 Cats at Shelter

Reported by: RNS

Saturday, Dec 20, 2008 @11:25am CST

Canadian authorities say mice were responsible for starting a fire that killed about 100 cats at an animal shelter.

The "Toronto Star" reports the 250-thousand-dollar blaze is still under investigation, but preliminary reports suggest it began from mice chewing through electrical wires.

Several rabbits and rodents also died in the fire but firefighters were able to save nine dogs.

While many flooded the shelter's website with donations, some are questioning why the animals were left unattended overnight.

According to the shelter's manager, it can't afford an overnight staff.

The eternal struggle

2008-12-16T05:55:00.000-08:00

Man's inhumanity to mouse, or what to do with too much time (and technology) on your hands.

http://www.baynesolutions.net/mouse/FirstContact.aspx

Note: Contains some four-letter words and depictions of violence against mice.

Gourmet Mice

2008-12-05T06:37:00.000-08:00

Police have seized 2,010 rounds of Parmigiano-Reggiano valued at over $1,000,000 from a warehouse in Parma, Italy. The cheese, nearly 80 tons of it, is being evaluated to determine if it is fit for human consumption after an infestation of mice was discovered. At least 29 of the cheeses had mouse tooth marks.

Grate that on your pasta and eat it.

Sources: here, here, and here.

Glow in the Dark Mice

2008-11-25T06:41:00.000-08:00

This year's Nobel Prize in Chemistry was awarded to scientists who took a fluorescent protein from jellyfish and developed a technique to tag proteins with it, "shedding light," so to speak, on countless biological processes. One of those scientists, Osamu Shimomura, writes here about the early days of that research, cutting up jellyfish and extracting the protein.

And here is an example of an application of that technique, with some surprising findings about stem cells:

Happy Birthday Mickey!

2008-11-19T05:57:00.001-08:00

The most famous mouse of all made his debut on November 18, 1928, in Steamboat Willie.

Walt Disney, who provided Mickey's first voice, had originally intended to call him Mortimer.

Imagine the theme song:

M-O-R-T Tea and scones anyone?
I-M-E-R Are you sure?

Page 56 Meme

2008-11-18T05:58:00.000-08:00

Thanks to QuakerDave, I finally have a meme I can do.

* Grab the book nearest you. Right now.
* Turn to page 56.
* Find the fifth sentence.
* Post that sentence along with these instructions on your blog (or Facebook wall).
* Don’t dig for your favorite book, the coolest, the most intellectual. Use the CLOSEST.

Here's mine:

"Stereocilia increase the surface area of the epithelium for absorption."

Oh, what a fascinating life I lead...

Tag, you're it.

It's Alive!

2008-11-07T05:56:00.000-08:00

Scientists in Japan have succeeded in producing healthy cloned mice from mice that had been frozen for up to 16 years.

Usually, when you clone an animal from a frozen specimen, that specimen has been intentionally frozen for future cloning. That means great care was taken to prevent the cells from rupturing and a cryoprotective agent (like polyvinylpyrrolidone or glycerol) was added to keep the membranes intact.

In this study, there was no cryoprotectant and the cells were not viable. The investigators managed to produce their clones using just the nuclear material, and not living cells.

This means that it may be possible to produce living clones from frozen specimens of animals that are endangered, or even extinct.

Like the woolly mammoth.

Here's the paper.

Lab humans

2008-10-21T07:08:00.000-07:00

Remember those mice on Mount Everest?

There may be a good reason for them to limit their mountain-climbing expeditions. It might shrink their brains.

Scientists have studied human mountain climbers and found reduced volume and density of white and gray matter in areas of the brain associated with motor activity.

It is not known if this phenomenon is relevant to mouse health, but it suggests that mice should use caution when participating in high-altitude activities.

Going to the happy place

2008-10-13T08:40:00.000-07:00

You can train a mouse to stress out on cue by having it associate a particular sound with an unpleasant experience, like a mild electric shock. A group of researchers at Columbia University did the opposite. They taught mice "learned safety" by having training them to associate a sound with the LACK of an electric shock.

Then they put the mice in the water and let them swim around. After a couple of minutes, mice usually stop moving around, apparently in despair, having lost the will to live. At least that's how scientists interpret that behavior.

As reported here (Here's the paper), mice trained in "learned safety" can regain their will to live when they hear their "happy sound" and they start swimming again. Apparently, mice can be trained to overcome depression.

And their brains showed some of the same biological changes seen in mice given antidepressant drugs.

Does this mouse have a happy place?

Feathered mice

2008-10-07T06:43:00.001-07:00

Because of its geographical isolation, New Zealand has a unique population of native animals. Until fossil evidence showed otherwise in 2006, it was believed that there were no mammals native to New Zealand that did not swim (marine mammals) or fly (bats).

No mice.

But there was an ecological niche that, in the rest of the world, was occupied by mice. In New Zealand, that niche was occupied by the flightless Stephen's Island wren (Xenicus lyalli). Its Latin name is taken from the lighthouse keeper who first described it scientifically, David Lyall.

The wren became extinct in 1894. Legend has it that David Lyall's cat, Tibbles, was single-handedly (single-pawedly) responsible for the demise of the Stephen's Island wren. It is more likely that the wren was hunted to extinction by feral cats or rats introduced to New Zealand by human settlers.

And who arrived to occupy that now-empty niche? Immigrant mice.

If your mouse is getting flabby...

2008-09-21T17:26:00.000-07:00

Agility training for hamsters (and rats, gerbils, mice and rabbits)

From the Milwaukee Examiner...

POSTED September 20, 6:46 PM

Teri Webster - Pet Examiner

Running Bear likes to spin his wheels.

Every day, he runs for miles on his hamster wheel and rides a motorcycle.

Well, he runs inside the large front wheel of his toy motorcycle, and that propels it around a small track.

But Running Bear is up for a new challenge, so he plans to start agility training.

His owner, Marna Kazmaier of Belle Fourche, SD, says that hamsters, rats, gerbils, mice and rabbits can learn to run -- or at least meander --over an agility course.

Many people may not know that hamsters can be trained just like other pets. At least that's what some proud "hammie" owners say.

The good news is that you don't have to teach them to bite. They do that on their own. Agility training takes a little more work.

Running Bear runs in the front wheel of his motorcycle.

"It's a lot of fun and easier than most people might think to train the little animals to run a course," said Kazmaier.

If you put a treat in your hand, most hamsters will follow it, Kazmaier explains.

"Hamsters, as a whole, are not agility course runners," said Kazmaier. "They kind of meander over the course, but they're cute all the same."

Hamsters do not jump over obstacles but climb over them so the pieces need to be stable, especially for bigger males, said Kazmaier.

More information on hamster agility training is available here.

Kazmaier also has Web sites for training gerbils, mice, rabbits and rats; "Bible Donkeys," and working goats and llamas.

Apparently, there isn't much to do in South Dakota...

"I had a chicken I taught to do a few tricks," Kazmaier said. "Training animals is kinda my thing."

According to the Web site MyHammie.com, you can teach your hamster to stand on its hind legs. Take a sunflower and hold it over the hamster's head and say the word "stand."

Eventually, you can just tell the hamster to stand without a treat, the Web site claims.

Right. And I can teach a "hammie" to fly.

More about finger length

2008-09-20T17:35:00.001-07:00

Let's take a closer look at that last post. The person who wrote the UPI piece didn't interpret the original paper the same way I did. The finger measurement they were using was the ratio between the length of the index finger (2D) and the ring finger (4D).

Since as early as the 19th century(1), people have noticed that men tend to have a lower 2D:4D ratio than women. Since then the ratio has been linked to a variety of sexual, psychological, and behavioral traits. The number tends to be lower for men, for people with greater athletic prowess, assertive women, engineers, mathematicians, and lesbians. So they call a lower number a "masculinized" 2D:4D ratio.

But it's different in mice. Mice with a HIGHER ratio are more aggressive, more likely to bite when handled, and have a higher daily level of activity.

In the study cited here, the investigators selectively bred mice to be more active; they selected the mice that liked to run in their wheels more and bred them to each other. Then they measured their fingers. Voila. They had a HIGHER 2D:4D ratio.

So does this mean that finger length has any biological implication for behavior, physical prowess, or sexuality? Here's what the authors said:

"Given the many factors that have the ability to affect digit ratio, it is clearly more complicated than a simple testosterone-driven manliness metric."

I couldn't have said it better. Yeah, there might be some hormonal thing going on, but as it stands, it's no more scientific than trying to guess what's going on in a person's head by mapping the bumps on the skull.

(1) Anthropological Notes on the Human Hand Frank Baker

American Anthropologist Jan 1888, Vol. 1, No. 1: 51–76.

How long are your fingers?

2008-09-18T11:43:00.000-07:00

From UPI.com:

Finger length linked to
desire to exercise
EDMONTON, Alberta, Sept. 17 (UPI) -- Canadian and U.S. researchers say there is a direct correlation between the length of fingers and being motivated to hit the gym.
Researchers at the University of Alberta and University of California-Riverside, who conducted a study using 1,000 white mice, said the findings seem to support a stronger connection between digit length, voluntary exercise and high levels of prenatal stress hormones -- indicated by the difference in activity level between the control mice and the selectively bred, active mice.

The study, published in the journal PLoS ONE, suggests prenatal stress, rather than prenatal testosterone levels in the womb, forms a component of the inherent desire for physical activity.

"The research shows a link, or relationship, between the brain, behavior and personality traits and the shape of the hand," lead researcher Peter Hurd of the University of Alberta said in a statement. "It opens the door to the notion that aspects of one's personality, in this case the desire to exercise, are fixed very early in life.

Here's the actual paper, from which the above photo was lifted.

The language of adolescent mice

2008-08-27T11:42:00.000-07:00

Different inbred strains of laboratory mice interact differently, suggesting a role for genetics in social behavior.

They may also speak a different language.

This paper examined behavioral differences between two common strains of mice during adolescence. In the wild, when young mice leave their mothers and head off on their own, they may do so in groups, and the social interactions between individuals in those groups may have survival advantages. The young mice also need to establish territory and find mates. In the study, adolescent C57BL/6 mice had more social interactions than age-matched BALB/c mice. The differences became less pronounced as the mice matured.

The investigators analyzed the mouse vocalizations, even the ones too high for the human ear to detect. (Remember the singing mice?). Vocalization was correlated with social interaction; the socially interactive C57BL/6 mice were more talkative than their BALB/c peers. The C57BL/6 mice also tended to make shorter, higher pitched vocalizations than BALB/c mice.

The investigators found modulations in pitch within each vocalization that reminded me of my disastrous attempt to learn to speak Chinese with all its inflections; upward, downward, complex.

This study also found that the two strains differed in the ways they modulated their vocalizations. For example, BALB/c mice were more likely to use upward modulation and C57BL/6 mice were more likely to use downward modulation.

I wonder if everything the BALB/c mice had to say sounded like a question.

Upcoming events

2008-08-24T18:03:00.000-07:00

Now that the Olympics are over, I thought some of my loyal readers would be interested in competitive events to be held in the near future:

6 September: London Championship Show, Rivermead Leisure Centre

20 September: Annual Cup Show, St Christophers Church Hall

12 October: Peterborough Agricultural Show

25 October: Swindon Mouse Club, Hermitage Village Hall

1 November: Greater Manchester Mouse Club, Methodist Church

22 November: Yorkshire Mouse Club

21 December: Stafford Poultry Show

These events are under sponsorship of the National Mouse Club. Although the phenomenon peaked in the Victorian era, fancy mice are alive and squeaking. As I have posted previously, fancy mice--mice bred for mouse beauty pageants--were instrumental in the introduction of mice into biomedical research. In fact, mice of the common breed C57BL/6 are direct descendants of fancy mouse number 57.

I'd love to attend the December 21 show, if only to see why the National Mouse Club would sponsor a poultry show.

Mouse Mouse

2008-08-15T15:37:00.000-07:00

When I'm cruising the web for blog fodder, I'm often confronted with the "other kind" of mouse. You know, the kind that makes your cursor move around. Well, here's how to marry the two concepts. Mind you, it's a little gruesome.

Really big rodents

2008-08-14T12:05:00.001-07:00

OK, it's not even September yet, and the scrabbling in the walls has started. Maybe the mice know something we don't know about an early winter.

At least it's not rats. I remember seeing some really big rodents hanging around the dining hall dumpsters in college. I'd hate to have those scrabbling in the walls.

If you want to see some really really big rodents, you need to get away from mice and rats and look at capybaras, which can weigh up to 140 pounds. Imagine the holes this guy could chew in your walls:

For some really really really big rodents, we can look to the fossil record and find Josephoartigasia monesi, which had a 21-inch skull and could have weighed as much as 2,200 pounds:

I don't think these things would scrabble in the walls. It would probably be more like this:

Guns don't kill people...

2008-08-04T13:38:00.000-07:00

From foxnews.com:

Woman Shoots Herself While Trying to Kill Mice

POTTER VALLEY, Calif. — A Mendocino County woman who was trying to kill mice in her trailer with a gun ended up shooting herself and another person.

The 43-year-old woman pulled out her .44-caliber Magnum revolver after she saw the mice scurrying across the floor of her trailer on Highway 20 in Potter Valley, sheriff's officials said.

But she accidentally dropped the gun, which went off as it struck the floor. The bullet went through the woman's kneecap, bounced off the keys sitting on the belt loop of a 42-year-old man in the trailer and grazed the man's groin before ending up in his coin pocket.

Authorities did not release the shooting victims' names.

The mice escaped the shooting unharmed.

Fly through a mouse brain!

2008-07-26T13:02:00.001-07:00

What do you do when you want to see what is inside a mouse's head?

In the past, you had to:
1. Find a mouse.
2. Kill said mouse.
3. Remove brain (the mouse's, not your own).
4. Fix brain (even if it wasn't broken to begin with) in formaldehyde or some other chemical.
5. Embed brain in wax.
6. Cut brain into teeny tiny slices.
7. Try to get one of those slices to sit flat on a slide.
8. Stain the brain slice.
9. Look at it under an expensive microscope.
10. Try to figure out what you are looking at.

Now, through the wonders of modern Interwebology, you need not go through the toil and trouble and smell. Now we have The Mouse Brain Library. For the librarians among my loyal readership, this is not the kind of library where you walk through the stacks until you find a brain on the shelves that might look interesting, then check it out with your library card.

No, indeed. This is the kind of library that lets you look inside a mouse's brain without leaving the comfort of your favorite coffee shop. You can even watch movies.

Here's my favorite. It's a trip through a mouse head, starting at the top and going down. This one shows structure of the surrounding head, as well as the brain. The nose is to the right and the back of the head is to the left. You can see the eyes, white circles at the top and bottom of the image. Between them lie the olfactory bulbs, responsible for smell. (The sense of smell that is. The smelliness comes from the other end of the mouse.) You can also see the spiraling chambers of the nasal cavities.

And that ends our tour through a mouse's head. I hope you enjoyed it. Watch your step as you leave the tour bus.

Yeah, but what happens if you smoke it?

2008-07-15T08:44:00.001-07:00

A compound in oregano and basil has been shown to have antiinflammatory effects in mice. The compound, called (E)-beta-caryophyllene or(E)-BCP, is also found in large amounts in rosemary, cinnamon, and black pepper. And Cannabis sativa, a.k.a. marijuana.

The most well-studied components of marijuana, cannabinol and tetrahydrocannabinol (THC), exert their effects by binding to two receptors, CB1 and CB2. CB1 is expressed in the brain and other tissues and is responsible for the ...elevating...effects of Cannabis sativa. CB2, on the other hand is primarily found in tissues outside the brain. Activation of CB2 has been shown to inhibit inflammation.

This paper describes some experiments showing that (E)-BCP binds to CB2, but not CB1. They did all the stuff you are supposed to do in the lab to demonstrate its binding qualities, then they tested the compound in mice.

They dissolved (E)-BCP in (appropriately) olive oil and fed it to mice. Then they injected the footpads of the mice with carrageenan, which makes the footpads swell. The feet of the mice that had been fed (E)-BCP had much less swelling than the mice that had been fed olive oil alone. This antiinflammatory effect was not found when they used mice in which the CB2 receptor had been knocked out, demonstrating that it was the CB2 receptor activation that was responsible for the beneficial effect.

I knew pesto pizza had to be good for you.

Did they make it to the top?

2008-07-01T07:01:00.001-07:00

Here's a story in the Philadelphia Inquirer about the murine Everest ascent.
Here's a blog about it.
Here's some video.

The answer: almost.
The real answer awaits the arrival of the mouse blood from Nepal...and some lab work. Not as glamorous as mountain climbing, I know, but that's science for you.

Don't believe everything you read

2008-06-28T12:31:00.000-07:00

Sara Latta brought this photo to my attention. I'm not going to reproduce it here. It's a prime example of what happens when people place their own agendas ahead of scientific accuracy.

On October 11, 1999, a nude mouse appeared in a full-page ad in The New York Times, sporting what appeared to be a human ear growing out of its back. The caption described it as “an actual photo of a genetically engineered mouse.” A group protesting unregulated genetic research had placed the inflammatory ad, but it was not exactly accurate. The mouse was not genetically engineered at all. It was a normal nude mouse. Nor was the ear human. It was a product of the laboratory of Charles Vacanti.

Vacanti wanted to improve replacement options for patients who have lost an outer ear (or other cartilage-based structure) due to injury, burns, or birth defects. Plastic implanted under the skin can become infected and is not very durable. An ear sculpted from the patient’s cartilage may not be shaped satisfactorily. Vacanti used a synthetic polymer, similar to that used in dissolvable sutures, to sculpt an outer ear. He then implanted it under the skin of a nude mouse, along with cartilage cells from the legs of calves. Because nude mice do not reject tissue from other animals, the calf cartilage cells could survive and grow in the nude mouse.

The mouse's body provided the necessary environment for the cartilage cells to attach to the polymer scaffold, eventually replacing the scaffold, which dissolved away. The result was cartilage in the perfect shape of a human ear.

Although the result was bizarre-looking, especially in the already bizarre-looking hairless mouse, it was very effective. The technique has since been used successfully in humans, producing replacement cartilage structures from human cartilage cells on polymer scaffolds implanted into the patient’s body.

The mouse was later to be called the Vacanti Mouse or the "earmouse." Unfortunately, its bizarre appearance was used to promote the anti-science agenda of the group that ran the ad. Take a photo out of context, add some half-truths and outright lies, and you can convince the public of almost anything.

That is why we need to promote scientific literacy.

Distant relatives?

2008-06-09T08:33:00.000-07:00

In response to a comment from Moonrat, I have done a bit of genealogical research, hoping to discover some long lost rodent relative. I was skeptical because Moonrat's appearance seemed to me to be more possum-like than rat-like. Quite reminiscent, in fact, of the opossum that sometimes engages in moonlight raids of my compost bin.

Alas, Moonrat is but a distant mouse relation. Native to the Malay Peninsula, Sumatra, and Borneo, the moonrat (Echinosorex gymnura), also called Raffles's gymnure, is an insectivore, more closely related to the hedgehog than the mouse.

Sorry there's no relation, Moonrat. Give my regards to your Aunt Tiggy-Winkle.

Where no mouse has gone before

2008-06-04T11:04:00.001-07:00

Yes, mice are climbing Mount Everest as I post. They look so cute in their little parkas, and you should see the tiny little crampons they are wearing on their feet!

OK, I made up the part about the parkas and crampons, but the rest is true.

Scientists from the University of Pennsylvania, led by Tejvir Khurana, are carrying lab mice to the top of the world. This article, from New Scientist, describes how the mountain-climbing scientists will be testing the mice for changes associated with extreme altitude. The ultimate purpose of the study is to find a way to detect athletic doping.

As I discussed in a previous post, athletes often train at high altitudes so that their bodies make more red blood cells, improving their performance. The hormone responsible for the increase in red blood cells is erythropoeitin, or EPO. In the past, doping athletes used synthetic EPO to boost their blood cells, but there is now a test that can distinguish synthetic from naturally-produced EPO. Dopers could potentially get past that hurdle by using other substances (like mustard oil?), or even genetic manipulation, to stimulate the natural processes that induce EPO.

The researchers hope to stay one step ahead of the dopers by identifying markers in the tissues of blood of mice at high altitude. These markers could then be used in an anti-doping test to identify natural EPO produced by unnatural means as opposed to natural EPO produced in response to the perfectly legal practice of training at high altitude.

Now that's a claim to fame I can live without: first scientist to bleed a mouse at the summit of Mount Everest.

I think I'll have a cup of hot chocolate, now.

A Twist of Lyme

2008-05-31T11:09:00.001-07:00

My dear husband, Smintheus, came home earlier this week looking less than his usual robust self. He soon spiked a fever. Since he had been camping and morel hunting in a Lyme endemic area the two previous weekends, I took him to the clinic for some doxycyline. Although he didn't have a documented tick bite, several in his party did, and the ticks are so small at that stage, they would be easily missed. The doctor agreed that it would be prudent to treat the disease as Lyme, since the blood test is often inconclusive and early treatment can prevent serious long-term consequences.

"Here she goes again," you say. "Another off-topic post."

Stay with me.

Lyme (not Lyme's) disease was named for the town in Connecticut where it was first identified. It is caused by the bacterium Borrelia burgdorferi, transmitted to humans by the black-legged tick, also known as the deer tick. This tick (Ixodes scapularis) has a complex two year life cycle. From the common name of the tick, you would expect to find them associated with deer, and they are.

But they also feed on mice, and it is the mice that are the source of the infection.

The ticks only take a blood meal two or three times in their lives. The first, which is usually from a mouse, allows it to mature from a larva to a nymph. It is the nymphal stage that is most likely to bite humans, especially in the late spring and summer. The second blood meal (which can be from a variety of animals, including humans) allows the nymph to mature into an adult tick. The female takes a third blood meal from a deer so that she can lay eggs.

Deer are important for the life cycle of the ticks and for carrying them around and spreading them through the environment, but they aren't infected by the Lyme bacterium.

It's our friend the mouse, specifically the white footed deer mouse (Peromyscus leucopus), that is the major reservoir. Up to 90% of mice in some areas are infected with the Lyme bacterium.

Here is a fascinating discussion of the ecology of Lyme disease and how the prevalence and transmission are affected by deer, mice, weather, acorns, and human behavior. Here is a paper (and a more user-friendly press release) about mouse vaccination as a way to interfere with the transmission of Lyme disease.

Ear Worm

2008-05-27T08:00:00.000-07:00

I know this is off-topic, but I have this tune I can't get out of my head. Maybe if I blog about it, I'll be rid of it.

I'm working on a piece on collagen and I keep thinking of that ad for College Inn chicken broth, you know:

"Homemade soup with collagen..."

It always struck me as a rather unappetizing commercial. I know there's collagen in soup, but it's not something you'd want to advertise.

You are what you eat (from)

2008-05-15T07:27:00.000-07:00

It's not just food that makes us fat.

In studies presented yesterday at the 16th European Congress on Obesity in Geneva, Switzerland, researchers have shown that exposure to certain chemicals early in life can promote obesity.

Three groups of researchers presented findings on the effects of endocrine disruptors, chemicals that mimic the effects of hormones, on the development of mice.

The chemicals include:

Bisphenol A (BPA), used in polycarbonate plastics, like plastic containers, plastic wrap, and the linings of food cans
Perfluorooctanoic acid (PFOA), a greaseproofer used in food containers, like microwave popcorn bags and pizza boxes
Tributylin, used in plastic food wrap

These chemicals can leach into food and has been found in the blood of people living in developed countries.

The researchers, from Tufts University, the EPA, and UC-Irvine, demonstrated that mice exposed to these chemicals in utero and early in life were fatter as adults than control mice, even when their food intake and activity level were the same. The exact mechanism of action is unclear, but the investigators noted differences in the ways these mice regulate glucose and respond to insulin, and in levels of the hormone, leptin. The effects were not seen when mice were exposed only later in life.

I was told as a new mother that bottle-fed babies have a greater chance of becoming obese than breast-fed babies, probably because they don't learn to regulate how much they eat. "Just finish this bottle, and we'll be done, sweetie." Or maybe it was because of certain ingredients in commercial baby formula. These studies make me think that it's not just what's in the bottle, or how much they drink from the bottle, but the bottle itself that predisposes to obesity.

EPO

2008-04-18T13:10:00.001-07:00

If you are a fan of the Tour de France bicycle race, you know all about EPO, or erythropoietin.

EPO is naturally found in the body and its normal function is to induce the production of red blood cells, or erythrocytes. Since the red blood cells carry oxygen, more red blood cells mean more oxygen available to the muscle, which in turn means improved athletic performance.

As a drug, EPO is used to treat conditions like anemia, but it can also be used (illegally) to boost an athlete’s red blood cell count. The Tour de France is a grueling race, and many are tempted to make it a little easier. If you are caught using EPO, you are kicked out. EPO is part of a long history of doping in the Tour, and cycling in general.

The body can make more EPO naturally, under conditions of low oxygen, or hypoxia. That’s why people living at high altitudes, where there is less oxygen, have more red blood cells. It's also why Tour de France competitors often train at high altitude.

Proteins in the lungs called hypoxia-inducible transcription factors (HIFs) sense the low oxygen and induce the production of more EPO to make more red blood cells. HIFs are also present in the skin of frogs. Since amphibians can breathe through their skin, this makes sense. What is surprising is that these people found HIFs in mouse skin, too.

They wanted to see if skin HIFs had any functional significance in mice, so they rigged up chambers in which they could control the oxygen content of the air the mice breathe independently of the air that contacts their skin. They found that low oxygen levels at the skin increased EPO, but not in mice in which HIF expression in the skin was knocked out. That means that HIFs in the skin are involved in hypoxia-induced EPO production.

Part of the skin’s response to low oxygen includes increased blood flow. When they applied nitroglycerine patches (which increase blood flow) to the skin of mice, EPO levels also increased.

Another substance that increases blood flow in the skin is mustard oil (allyl isothiocyanate). This also increased EPO in mice. The authors note that it is common practice in Pakistan and Nepal to massage the skin of newborns with mustard oil and they speculate that this practice might increase the production of EPO and thus red blood cells in the babies. (Here’s the paper.)

So the next time you smell mustard oil at the Tour de France, you will know why.

Mind control

2008-04-03T07:58:00.000-07:00

Yesterday, I wrote about how male mice respond to the smell of the urine of female mice—they sing.

The subject for today is bobcat urine and how an infection can change a mouse’s response to it.

Normally, when a mouse smells a cat (or a fox), it runs away. I mean, it makes sense, given the gustatory preferences of cats. It’s pretty Darwinian, too. Mice that run away when they smell a cat are more likely to survive than mice that hang around.

Toxoplasma gondii is a parasite that can infect mice, cats, and humans. It’s the reason pregnant women are advised not to change their cat’s litter box. Here’s why:

The life cycle of the parasite requires that it spend some time in cats, to undergo the sexual portion of its reproductive cycle. Normally it gets into cats when cats eat an infected mouse.

This paper describes how Toxoplasma gondii makes it more likely that it will complete its life cycle. It controls the minds of mice. The investigators studied both rats and mice infected with Toxoplasma gondii. Control animals spent as little time as possible near bobcat urine or a collar that had been worn by a cat. Infected animals spent more time near the catty items. Not only were they not afraid of cat smells, they were attracted to them.

This wasn’t just a generalized anxiety effect, and it was specific for predator smells. Infection didn’t affect their behavior around rabbit urine or novel foods.

The parasite changes the brains of mice in such a way that the mouse is attracted to the very predator that is required for the parasite to reproduce.

There is even some evidence that Toxoplasma gondii infection affects human behavior, and that it may play a role in schizophrenia.

Yet another reason to stay away from cat poop.

If you're happy and you know it...

2008-04-02T11:39:00.000-07:00

Male mice make ultrasonic vocalizations that, when slowed down enough for us to hear, sound like songs. Listen here.

This study looked at what makes them sing. The answer: female mice.

They sing when they smell the urine of female mice, but not rats or humans.

They sing when they can touch female mice, but not if they can only see them.

And they sing when they are...um...interacting with female mice.

But they don't sing as much when certain brain receptors have been knocked out.

Muscarinic receptors (in this case M2 and M5), are necessary for dopamine release. Dopamine is a neurotransmitter that plays a role in motor control, emotion, sexual behavior, and scads of other functions.

If you don't have dopamine, you are not happy.

So mice without M2 and M5 receptors are not happy and they aren't likely to sing. I wonder if they only sing the blues.

Now let's see what drugs can do. (Mice on drugs!) When they give these guys amphetamines, which activate dopamine, they sing more. Except if they have had the M5 receptor knocked out.

The authors propose that ultrasonic vocalizations can be used to measure positive affect in mice.

In other words, you can tell how happy a mouse is by listening to it sing.

Here's the paper.

It's a gas

2008-04-01T06:37:00.000-07:00

Meet Joseph Priestley (1733-1804).

He discovered the pencil eraser and carbonated water, essentials for Sudoku and Diet Coke, respectively.

Aside from those critical discoveries, his most important contributions to science had to do with the chemistry of air. He is generally known as the discoverer of oxygen, but it was Priestley who first proposed that air is not a single element (as in air, water, earth, and fire), but was made up of a mixture of gases.

Priestley may have been one of the first scientists to use mice in research. Using a candle, a mouse, and a sprig of mint, he demonstrated that oxygen (as it was later dubbed by Antoine Lavoisier) is needed to keep a candle alight and a mouse alive. He also showed that, although flames and mice use up oxygen, plants produce it. That's photosynthesis.

He discovered a lot of gases. Along with oxygen, there was carbon dioxide, carbon monoxide, ammonia, nitrous oxide (laughing gas), and hydrogen sulfide.

Hydrogen sulfide is the gas that give rotten eggs their rotten smell. High doses are lethal. A recent study has shown that when mice inhale small doses of hydrogen sulfide, their hearts and metabolisms slow down and their bodies use less oxygen. (Here's the paper.) It's like hibernation, but without the cold. Some also call it suspended animation. The effect is completely reversible with no apparent ill effects.

Hydrogen sulfide allows mice to survive in conditions of low oxygen. If it's true (and safe) for humans, too, then it could buy some precious time in the ER.

Back to the eighteenth century. Not only did Priestley demonstrate that oxygen kept mice alive, but more was better. Extra oxygen added to the glass chamber enhanced mouse survival.

"Had it been common air, a full-grown mouse, as this was, would have lived in it about a quarter of an hour. In this air, however, my mouse lived a full hour; and though it was taken out seemingly dead, it appeared to have been only exceedingly chilled; for, upon being held to the fire, it presently revived, and appeared not to have received any harm from the experiment."

He also tried some of this stuff himself and felt "peculiarly light and easy for some time afterwards." A man truly ahead of his time.

Mouses in Houses

2008-03-19T17:39:00.000-07:00

Mice are very adept at invading our homes. Even if we never see them, a new study suggests that they may have left their calling cards, to the detriment of our health.

This article describes a study in which investigators found detectable levels of mouse allergens in 82% of the 800 homes they sampled. They suggest that mouse allergen might be an unrecognized trigger for asthma.

The allergen was most frequently found on the kitchen floor. Understandable.

Allergen was also commonly found on beds. Ick.

I have anecdotal evidence of mice in my house (see this and this), so I imagine my house is chock full of allergen, which can't be good for my asthma.

The solution might be obvious...get a cat.

But I'm allergic to 'em.

Surfing Mice

2008-03-13T19:35:00.001-07:00

What can I say?

Spiny Mice

2008-03-13T11:51:00.000-07:00

For 100 years, scientists have been studying mice in the laboratory. Usually they are the highly inbred kind, like albino Balb/c mice or black C57BL/6 mice. Often, they have been genetically manipulated in some way to serve the purposes of the investigators. But basically, they are still the same thing. Lab mice.

Some experiments call for a different kind of mouse. Here's a study that uses spiny mice (Acomys cahirinus). From the picture above you can see that they are not your typical lab mice. Their eyes are bigger, for one thing, like those of wild mice. (Lab mice seem to have lost the visual acuity of their wild cousins, not needing to see and avoid predators to survive.)

They are called spiny mice because their guard hairs are stiff, giving them a prickly coat. Mind you, I've never touched one, myself. Some say they are related more closely to gerbils than to mice.

Why use these mice instead of cheap, available, run of the mill lab mice? The study looked at the the ability of the pups to tolerate oxygen deprivation at birth. They used spiny mice because they are more mature at birth than lab mice, more like human babies. Their eyes are open, for example, and their brains are more developed.

As for the findings, the pups were protected from brain damage by supplementing the diets of the pregnant mothers with creatine, that stuff that body builders take to bulk up their muscles.

I could make a comment here about the brains of body builders, but I won't.

In Search of 3,200 White Females

2008-03-06T05:31:00.000-08:00

White female mice, that is. And they must weigh between 16 and 18 grams.

In a story that's circulating around the blogosphere, Russia's Federal Guard Service has placed an ad offering $20,000 for these mice, without specifying a reason for the request.

Theories have been proposed about the potential fate of the mice, ranging from falcon fodder to mini-spies outfitted with mini-cameras.

But why white?
I don't imagine a white mouse would make a good spy, as it would not blend in very well.

And why female?
Do falcons prefer the taste of female mice?

Is it for science or skulduggery?

Or is it just something to catch the interest of bored bloggers?

Barenaked Mice

2008-02-25T16:26:00.000-08:00

Nude mice are the result of a spontaneous mutation first observed in Scotland in 1962. These bizarre creatures have no hair, so they look pink and wrinkled, like elderly aliens.

They are also athymic, which means the thymus is absent. The thymus is the organ responsible for the development of T cells, those all-important soldiers of the immune system. Nude mice are soldier-deficient and are unable to defend themselves against infectious disease. At first, the most remarkable result of being athymic was that they died young. Later on, once researchers figured out how to keep germs out of their cages, the nude mice survived just fine.

What good is a nude mouse? You can study how the immune system works. That is important in itself. But the real starring role for nude mice is in xenotransplantation. Because they don't have the cells they need to reject foreign tissue, they will accept grafts from unrelated mice, and from cats and chickens (they grow feathers!) and lizards and frogs...and humans. Big deal, you say, a mouse with feathers.

It is a big deal. Nude mice will accept grafts of human cancer cells so we can study how to treat human cancers. Because they accept grafts of human cells, they can be used to study viruses that are difficult or impossible to grow in other animal models or in lab dishes, like hepatitis C virus and the human papilloma virus, which causes cervical cancer.

Why am I writing about nude mice? In a blatant attempt to increase traffic to my blog.

Someone may be looking for something a little more titillating and a little less immunological. I have been frustrated in many attempts to research nude mice. When I Google "nude mouse," I get a lot of "Our All-Nude site is just a mouseclick away..." Imagine my results when I try to find a photo of a nude mouse, or a story about nude mouse models for human diseases. You guessed it, photos of nude models with just the click of a mouse.

Turnabout is fair play.

To those who came to my blog looking for photos of nude models of the human variety: Thanks for visiting. I hope you learned something.

What if Morgan Spurlock were a mouse?

2008-02-21T13:22:00.000-08:00

If you give a mouse a Big Mac, does he get fat? If the Morgan Spurlock documentary “Super Size Me” is any indication, it’s highly likely.

So here’s a scientific study that answers that question, although that was a small part of the study. A group of scientists the Max-Planck-Institute for Evolutionary Anthropology in Leipzig, Germany used mice to study the differences between humans and chimpanzees. More specifically, they looked at the effect of diet on gene expression. The paper is here.

They took four groups of genetically identical mice and fed each group a different diet.

One group got the Mouse Diet: standard mouse chow.

A second group got the Chimpanzee Diet: fruits, vegetables, and yogurt usually fed to chimpanzees at the Institute.

The third group got the Scientist Diet: the food served in the Institute’s cafeteria.

A fourth group got the Morgan Spurlock Diet: straight from McDonald’s.

The most scientifically significant result had to do with gene expression. Each human, mouse, or chimp has a genome, a set of genes with the DNA blueprint that dictates which proteins that animal will make. The thing is, not all of the genes are used all of the time in every cell. You don’t want your heart to grow a mustache, for example, or your earlobes to be made of bone. The key is to make the right proteins at the right time in the right place. That’s gene expression.

Humans and chimps and mice have different genomes, different blueprints. But they’re not really all that different. What adds to the differences between species is the way the genes are expressed. The mystery is what causes these differences in gene expression.

The researchers at the Max-Planck Institute hypothesized that diet could affect how genes are expressed. What they found was that the livers of mice fed different diets expressed the genes in their livers differently. What was really cool was that 117 genes expressed differently in mice fed the chimp diet vs. the human diets were the same genes that are expressed differently in chimpanzees vs. humans. That means that diet affects how we express genes and is part of what makes humans different from chimps.

Notice that I said “human diets.” For the most part, the Scientist Diet and the Morgan Spurlock Diet produced the same results. (I wonder what they serve at that cafeteria.)

There were two differences. One was that, although gene expression in the livers of mice fed both human diets was pretty much the same, the Scientist Diet didn’t affect gene expression in the brain. The Morgan Spurlock Diet did. Fast food changes your brain. Scary.

The other difference was that after two weeks on the Morgan Spurlock Diet, the body weights of the mice were significantly greater.

Surprise.

Jet-Set Mice

2008-02-11T12:18:00.001-08:00

Last month, 7,000 lab mice got the royal treatment after the truck they were riding in was in an accident in Wyoming. The mice were en route from The Jackson Laboratory in Bar Harbor, Maine (The Mouse Capital of the World) to laboratories on the West Coast. Since the mice were so valuable, officials decided to box them up, 20 to a crate and fly them in three Lear jets to their destination. I wonder if they were served champagne.

Reports vary on their monetary value, from $100,000 to $6,300,000. Apparently some of the mice were worth $900 each. That's a lot of money for a lab mouse. Your standard C57BL/6 (or, as it is more commonly known, "Black 6") mouse costs about $15. Some reporter did the math, assuming they were all worth $900 (900 x 7,000 = 6,300,000). In reality, very few scientists could afford to use $900 mice. It's likely that just a few of the mice were that expensive. Hence, the revised figure of $100,000 to $250,000. Maybe they were served Miller Lite.

The Original Sminthia

2008-02-07T11:04:00.000-08:00

It started in a barn.

Forced to retire from her teaching job because of pernicious anemia, Abbie Lathrop made a career switch in 1900, at the age of 32. She became a purveyor of “fancy mice.”

The Victorian fad of Fancy Mice was in full swing. The mice were not particularly fancy, but they were fancied. In other words, the Victorians fancied their mice. They bred them for their beautiful or unusual appearance or behavior. (Remember The Spinning Mice?) They entered them in competitions, like Prize Poodles at the Westminster Kennel Club dog show.

Abbie thought she would cash in on the craze, so she began breeding mice in her Granby, Massachusetts barn. Among her “Creams,” “Tans,” and “Silver Fawns,” she noticed something unusual. Some of her mice had cancer.

She struck up a collaboration with Dr. Leo Loeb, with whom she authored ten scholarly papers. Here’s a quote from one of them:

In 1907 we published some observations made on the mouse farm of Miss Lathrop, in Granby, Mass., which rendered it probable that the frequency of tumors in mice at certain places was in all probability due, not to infection, but to hereditary transmission in certain families.

The rest, as they say, is histology…

Read the paper here. All 28 pages of it.

Commensal Mice

2008-01-27T17:11:00.000-08:00

Here's an excerpt from an article I read yesterday in New Scientist (in my opinion, the best science magazine out there):

Beastly tales: Rewriting human history
by Bob Holmes, 19 January 2008

ACCORDING to the history books, the Madeira archipelago 600 kilometres west of Africa was discovered in 1419 when Portuguese mariners were blown off-course by a storm. In Roman times Pliny and Plutarch wrote about islands that might be Madeira, but there is no definite account of the islands, nor any signs of people, prior to the arrival of the Portuguese. The mice of Madeira Island, however, tell a different and unexpected story.

The mice are not native to the island and must have arrived on European ships. Genetically, they most closely resemble the mice of Portugal. However, some of their DNA has strong similarities to that of mice found in Scandinavia - a strong hint that Viking ships found Madeira long before the Portuguese. "It might have been a temporary occupation, or just a few boats landing for a short period of time," says Jeremy Searle, an evolutionary biologist at the University of York in the UK and an author of the study (Heredity, vol 99, p 432). "But the mice are telling us something that no artefact so far has told us."

What this piece is saying is that human history can be uncovered by looking at the plants and animals that accompany us, either as stowaways or as sources of food. Those commensal mice that have been a part of our lives since humans first started storing grain, have been following humans on their migrations around the world.

It's not just lab mice that have been teaching us about ourselves.

Here's a link to the original paper. Here's more about Archaezoology.

BTW, "kilometres" and "artefact" are explained by the London address on the masthead.

The Sminthophobe

2008-01-16T10:00:00.001-08:00

There were mice scrabbling in my walls yesterday evening, so what did I do? I went running to my Dear Husband, Sminthius, to come to my rescue. He set some traps in the attic, but I was still awakened at four am by the sounds of scratching and gnawing.

How many lab mice have I handled in my life? I daren't count. Why can't I stand a mouse in my house? I'm a sminthophobe.

Lab mice and wild mice are very different animals. (I could write a book...)

In fact, wild mice are very different from each other. Of course there are different species, but they can be classified another way, by their relationships with humans.

Truly wild mice, ABORIGINAL mice, live their lives completely independently of humans. They don't eat our food or invade our homes. They may never have contact with humans or our stuff at all.

COMMENSAL mice, like the ones in my ceiling, rely on humans for food and/or shelter, even if it's only for a part of their lives (like winter).

FERAL mice are mice that used to be commensal, but have abandoned their human neighbors and "gone native."

So now you know.

I still want them OUT OF MY HOUSE!

Waxing Political

2007-12-18T05:46:00.000-08:00

Count me in.

I'm joining the call for a Presidential Debate devoted to science and technology. How can our leaders make informed decisions about the multitude of issues that face us if they are ignorant (or worse, misinformed) about the science and technology behind them?

Some of these issues (plucked from the ScienceDebate site) include:

The Environment

» Climate Change
» Conservation and Species Loss
» The Future of The Oceans
» Fresh Water: Drought, Pollution, Ownership
» Population Growth and Its Effect on Environment
» Renewable Energy Research

Health and Medicine

» Global Diseases and Pandemics
» Stem Cell Research
» Antibiotic Resistant Bacteria
» Drug Patents, Generic Drugs
» The Genome
» Bioethics

Science and Technology Policy

» Scientific Innovation and Economic Growth
» Improving Science Education
» Space Exploration
» Preserving Scientific Integrity in Government
» Energy Policy

Decisions must be made based on solid scientific evidence-- not economic self-interest and not partisan politics.

Join me and spread the word.

Mice on Drugs!

2007-12-08T14:30:00.001-08:00

Look inside the brains of mice on drugs!

This is a cute animation from the University of Utah Genetic Science Learning Center. It shows mice on various recreational drugs--heroin, ecstasy, marijuana, methamphetamine, alcohol, cocaine, and LSD.

I think the mouse on ecstasy is supposed to be dancing. The mouse on cocaine looks pretty nervous.

You can pick up each doped-out mouse and "look into its brain." The descriptions of the effects of the drugs on neurotransmitters and receptors in the brain are very well done.

Who says neuropharmacology can't be fun?

The Energizer Mouse

2007-11-10T14:35:00.000-08:00

It just keeps going and going and going...

Researchers at Case Western Reserve University have engineered a mouse that makes loads of an enzyme called phosphoenolpyruvate carboxykinase (PEPCK-C) in their muscles. The mice can perform strenuous exercise for long periods of time without the troublesome buildup of lactic acid (that stuff that makes your muscles ache after you play a game of Ultimate Frisbee with people half your age).

"They are metabolically similar to Lance Armstrong biking up the Pyrenees," said Richard W. Hanson, senior author on the paper, published here.

It's not just their metabolism that amazes me. I mean, how do you get a mouse to WANT to run for that long? Just like the Tour de France, a large part of this Tour de Mouse seems to be psychological.

EEK!

2007-10-19T05:25:00.000-07:00

I must admit that my scientific aplomb and journalistic detachment went out the window this morning when a mouse peeked out from behind my shower curtain.

Gotta mouse-proof the house for the winter...

How to knock out (or knock in) a gene

2007-10-18T05:44:00.000-07:00

Check this out:

The video is divided into two parts. The second method (which begins 50 seconds into the second half of the video) is the Nobel Prize-winning technology of gene targeting.

This video comes from the Howard Hughes Medical Institute, the best thing Howard Hughes ever did. They support important research and also make some great stuff available (for free) to anyone who wants it: a magazine, videos, and a very cool series of CD-ROMs that let you pretend you're working in a lab, without the expensive supplies, toxic chemicals, or aching back.

Hail the Nobel Mouse!

2007-10-09T14:01:00.000-07:00

This year's Nobel Prize in Physiology or Medicine was awarded to Oliver Smithies, Martin J. Evans, and Mario R. Capecchi "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells."

Sounds pretty boring huh? Well, it's not. It changed biomedical research forever.

Before this work, which began in the 1980s, mice were used to study human biology and disease, but luck played a big role. Random mutations would sometimes result in a mouse that showed some kind of abnormality that mimicked a human condition--a tendency for obesity or cancer, for example.

Researchers could increase the rate of mutation with chemicals or radiation, but they couldn't control where the mutation would occur...until 1989. That's when gene targeting began, and this is how it works. Now scientists can introduce specific mutations into specific genes. What's more, they can control when and where the mutations are expressed. They can also inactivate a gene completely in what are called "knock-out" mice. What better way to determine the function of a gene than to inactivate it?

By now, thousands of mouse genes have been knocked out, and hundreds of new mouse models for human diseases have been created. The mouse genome has about 30,000 genes, and the plan is to knock them all out. In doing so, we can learn the function of each mouse gene, 90% of which have human counterparts.

So here's to the Nobel laboratory mouse. What a knockout!

Aspergian Mice

2007-09-12T11:25:00.000-07:00

UT Southwestern Medical Center researchers have developed a new mouse model for autism. Studies on humans have shown an association between autism and mutations in a protein called neuroligin-3. The researchers engineered mice with a similar mutation.

These mice were socially impaired. What they mean by that is that the mice spent the same amount of time as control mice interacting with a novel inanimate object, but spent less time than controls interacting with a novel caged mouse. There was no change if the other mouse was not kept apart from the mutant mouse, presumably because the other mouse took the social initiative. I wonder what would have happened if they put two mutant mice together...would they ignore each other? (They don't seem to have performed that experiment.)

The mutant mice were also smarter. They performed better in tests of spatial memory, like remembering where an object is.

The neuroligin-3 knockout mouse model is a much better model than this one, which had a lot of other problems.

They say it is a model for autism spectrum disorders, but I think it's more specifically a model for Asperger's syndrome (which is on the autism spectrum). Many Aspergians don't fit into our concept of normal socialization; they would rather spend time with inanimate objects than other people. They are also often cognitively gifted.

So the mice are better at one task and worse at another. Does that make them impaired, abnormal, disabled...or just different?

Off Topic

2007-09-12T11:14:00.000-07:00

OK, so this isn't about mice in biomedical research, but there is a mouse in the video.

This song was playing everywhere during a wonderful three-week vacation in France in 2001.

Maybe that's why I like it so much, but you have to admit, it's a catchy tune.

Buff Mice

2007-08-29T07:41:00.000-07:00

Se-Jin Lee from Johns Hopkins has made mice more muscular. (How's that for alliteration?)

It had been previously shown that mice engineered not to make myostatin are more muscular than normal mice. Mice that make extra follistatin also have big muscles. Dr. Lee generated double mutants, mice that make no mysotatin and extra follistatin. To his surprise, the effect was additive and the mice were even more muscular.

Understanding the molecular pathways that control muscle growth could lead to new treatments for muscular dystrophy. In fact, Dr. Lee's research was funded in part by the Muscular Dystrophy Association, Jerry Lewis's favorite charity. Good timing, Dr. Lee, since the telethon is this weekend!

You can read the original paper here.

The Spinning Mice are Loaded

2007-08-29T06:53:00.000-07:00

OK, I think I finally managed to upload the video of The Spinning Mice.

Let me know if you can get it to work.

The accidental compulsive

2007-08-28T11:15:00.000-07:00

Researchers at Duke University Medical Center may have stumbled upon a new mouse model for a human psychiatric disorder.

While studying how nerve cells connect and communicate with each other, the group, turned off a gene in the area of the brain called the striatum, which shuttles messages from the cerbral cortex to other parts of the brain.

Much as people with obsessive-compulsive disorder (OCD) may wash their hands repeatedly, the mutant mice groomed themselves incessantly, to the point where they injured themselves.

Some people with OCD are helped with selective seratonin reuptake inhibitors (of which Prozac is an example). When they gave the drugs to the mutant mice, the grooming stopped.

We have no way of knowing what these mice are thinking. ("Did I remember to turn off the stove? Maybe I didn't. I'd better go back and check again...and again...and again.") But it's a start.

Read the news story from Nature here and a story from Scientific American (with a photo of an overgroomed mouse) here .

Spinning Mice

2007-08-13T09:17:00.000-07:00

I found this cartoon from 1935.

The live action part of the film shows what I believe to be actual
Japanese Waltzing Mice. The literature describes them as white with
black markings and their behavior also seems to match published
descriptions.

The cartoon version of one of the mice says "Nature intended me to spin
and I'm gonna leave well enough alone."

The cartoon tells the story about what is either a scientist or a
wizard (He wears a very Harry Potter hat). This guy transforms "ugly"
animals into "beautiful" ones. Lizards into doves, for example. Then
some new ingredient is accidentally added to the mix and it turns a
cage of spinning mice into devils who make a new potion and turn the
man into a giant rabbit.

The doves (that used to be lizards) save the day and make a new potion
that turns the man and mice back to ther original states. The man tears
up his book, singing:

"The knowledge in that book of mine
Is better left unknown
And as for this my motto is
Leave well enough alone."

So the lesson is that you can't/shouldn't improve on nature. Funny, it was
the "improved" lizard/doves that saved the day. And nobody bothered
to change them back into lizards.

The old song and dance

2007-08-07T11:58:00.000-07:00

We've known about dancing mice for a long time. In the 19th century, Japanese Waltzing Mice were imported to Europe, to the delight of European mouse fanciers. The mice didn't really dance, but spun around nearly continuously due to an inner ear defect. It wasn't in 3/4 time, but it was a novelty and breeders continued to propagate the strain.

Japanese Waltzing Mice were important participants in nascent genetic studies of mice in the beginning of the 20th century.

Singing mice are new. Well, they've probably been singing all along, but we just haven't heard them. Male mice sing in the presence of female mice, but at a pitch too high for the human ear to hear.

Care to have a listen? Here's a little ditty. Here's something a little more operatic.

Three ways to make a schizophrenic mouse

2007-08-02T11:54:00.000-07:00

One from the University of Texas
One from Johns Hopkins
One from MIT (Déjà vu! It's our old friend Susumu Tonegawa again.)

Fearless Mice

2007-08-01T13:57:00.000-07:00

Scientists at the University of Iowa have produced fearless mice. Normal mice are fearful of open spaces, loud noises, and predators. (At least we think it's fear. They freeze.) But when the team, led by John Wemmie, disrupted the gene for an acid sensing ion channel protein (ASIC1a), the mice had reduced responses to the fearful stimuli.

Control mice froze when a beaker containing the scent of a fox was introduced into their environment. They stayed away from the beaker. Mice with the disrupted ASIC1a gene didn't freeze as much and even climbed onto the beaker. (Yes, they checked. Their sense of smell was normal.)

Now, these are lab mice. They have never seen (or smelled) a fox before. The researchers were studying innate (hard-wired) fear, not learned fear responses.

Here's the part that gets me. They also used a substance that blocked the ASIC1a protein (in normal mice). That also reduced the fear response. This substance, TcTx1, was isolated from the venom of Psalmopoeus cambridgei, this tarantula:

It grows to be five inches across, bigger than any mouse I've ever seen. I don't know about you, but no amount of spider venom will reduce my innate fear of this thing.

More Déjà Vu...Autism Cured in Mice!

2007-07-31T07:45:00.000-07:00

A group of scientists led by Susumu Tonegawa at MIT (Where have I heard that name before?) have demonstrated the first successful treatment for Fragile X Syndrome (FXS), a cause of mental retardation and autism. In mice genetically engineered as a model for FXS, they used genetic techniques to inhibit an enzyme called p21-activated kinase (PAK). Inhibiting PAK resulted in structural changes in the nerve cells as well as improvement of behavioral abnormalities.

This is not to say that we will be able to cure autism by genetic engineering, but there are drugs that inhibit PAK, and they might be useful for treating some kinds of autism.

Let me emphasize that FXS is only one cause of autism and mental retardation. The causes of the wide range of conditions along the autism spectrum remain unknown and have been the source of much controversy.

An interesting dialogue about the subject, including whether autism should even be “cured” at all, can be found here.

Here's the BBC story.

Here's the original paper.

Here's more than you would ever want to know about FXS.

Déjà vu in mice?

2007-07-31T07:43:00.000-07:00

Neuroscientist Susumu Tonegawa at the Massachusetts Institute of Technology (MIT) has reported on a mechanism for déjà vu (French for “already seen”). We’ve all experienced it, that feeling that you’ve been somewhere, or seen something before, even though...

Wait a minute. I get a feeling I’ve already posted this piece.

I have.

But I also had a little bit of déjà vu when I first saw this article. I knew I’d seen that name before. It didn’t take me long to figure it out. Susumu Tonegawa won the Nobel Prize in 1987 for his work (in mice) on antibody diversity.

Tonegawa’s work had solved a problem that had perplexed scientists for years. Antibodies are proteins that attack invading germs (and other things) very specifically. An antibody can tell the difference between two very similar molecules. How can the body make antibodies that are so specific? If, as was thought at the time, each protein was coded by a different gene, it would require millions of genes just for making antibodies. There are only about 30,000 genes in the mouse.

The solution was elegant. Antibodies are made up of two kinds of proteins called heavy and light chains. Let’s just look at the heavy chain for now. Each heavy chain has a constant portion and a variable portion. It is the variable portion that binds to foreign substances. The gene for the heavy chain also has a constant portion, but the portion that encodes the variable portion is the part we’re interested in.

The variable portion can be divided into three parts, V, D, and J. There are hundreds of copies of the V part of the gene, each with a different sequence. There are 20 different D segments in humans (12 in the mouse) and 4 different J segments.

To make an antibody, you take one V segment, one D segment, and one J segment. That gives you tens of thousands of different combinations. The segments don’t always join up in the same way, adding more possibilities. Add to that different light chains with similarly arranged variable regions and there you have it—antibody diversity.

Déjà vu in mice?

2007-07-31T07:42:00.000-07:00

The basis for this feeling, according to Tonegawa, is that you are really experiencing something very similar to something you’ve experienced before, but your brain can’t tell the difference. The part of your brain that helps you distinguish between two very similar experiences is the dentate gyrus. Tonegawa bred some mice in which the dentate gyrus doesn’t function very well and these mice were less able to distinguish between two similar situations than control mice.

As we age, the dentate gyrus becomes less functional, which explains why déjà vu happens more frequently as we get older.

Clyde Keeler and Apollo Smintheus

2007-07-31T07:36:00.000-07:00

Clyde Keeler went to Asia Minor to collect mice and search for new mutations. He claims that he was captured and tried for espionage in Turkey. Apparently officials found it hard to believe Harvard University would send someone so far just to catch mice.

He also had the chance to visit the temple on Tenedos:

“I wondered about the tiny Island of Tenedos at the mouth of the Dardanelles where stood the temple of Apollo God of Mice (Apollo Smintheus) since long before the Trojan War. Aristotle and other ancient writers told of the white mice raised under Apollo's altar. I went to Tenedos in 1930 and learned that in 1929 an albino house mouse was living in a garden shed a stone's throw from the site of the ancient temple of Apollo. Barring possible mutation, that could mean as much as 3,000 years of population inbreeding and with three generations a year the number of generations is staggering.”¹

This cult started around 1400 B.C. and continued until at least A.D.1453. In comparison, modern strains of laboratory mice have been inbred for about 100 years. I wonder if any descendants of the sacred mice of Apollo Smintheus are still wandering about Tenedos. Now that would be an interesting genome to sequence!

To whet your appetite for more, here’s a juicy tidbit from the world of laboratory mice: Super-sized mice

¹Keeler, Clyde, “How it began” In: Morse, H.C., III, (Ed.) (1978) Origins of Inbred Mice. Academic Press, New York. http://www.informatics.jax.org/morsebook/

Apollo Smintheus—The Mouse God

2007-07-31T07:34:00.000-07:00

There is a temple on the island of Tenedos dedicated to Apollo Smintheus, the Mouse God. According to Clyde Keeler, the cult of Apollo Smintheus thrived for 3,000 years. It all began when soldiers from Crete invaded Asia Minor and were victorious because mice had gnawed through the leather straps of their enemies’ shields.

Living in the temple were strange creatures—white mice. They scampered unmolested throughout the temple and were used to predict the future. According to Pliny “By the learning of soothsayers, observed it is, that if there be a store of white ones bred it is a good signe and presageth prosperitie.” (Quoted in Keeler, C.E. (1931). The Laboratory Mouse. Its Origins, Heredity and Culture. Harvard University Press, Cambridge.)

To finish up today's post, here are a couple of recent studies using mice:

Making a smarter mouse

Immunization against diabetes

Baldness cured in mice!

2007-07-31T07:31:00.000-07:00

Well, not exactly, but scientists at the University of Pennsylvania School of Medicine have shown that mice with skin wounds can regrow hair. Something about the healing process caused the cells in the healing wound to “open an embryonic window,” and do things that can normally only be done in an embryo, like making hair follicles. Stem cells were recruited to the area and formed new follicles, just as they are formed in the embryo.

Although this might eventually lead to a new cure for baldness (which would certainly please some), it also could lead to more medically important developments, like improved wound healing.

What is most intriguing, at least to me, is that this is the first time anyone has demonstrated actual tissue regeneration in mammals. Some animals, like salamanders, can regenerate an entire limb or a tail, but the only kind of regeneration shown to occur in mammals (up to now) requires some fragment of the original tissue.

Clyde Keeler, the man who named this blog

2007-07-31T07:26:00.000-07:00

Keeler introduces his 1931 book as follows:

“Small rodents will always find a place in the laboratory of the zöology teacher, the biological investigator, the medical researcher, and the fancier. Each man has different problems in mind: behavior, physiology, disease, and beauty among others...”

I’ll give him the benefit of the doubt on the “Each man” thing, since this was 1931, but there were actually women involved in mouse research even in the dark ages of the twentieth century.

“...Literature upon the house mouse, its origin, history, distribution, development, the nature of its variations, the hereditary transmission of its varietal characters, and methods of rearing it suitable to the needs of laboratories, has not been assembled so far as I am aware...To collect such valuable information as this concerning the house mouse and to present it in a usable form is the task of this book.”

I’m not sure how valuable Keeler’s recipe for mouse food is today (240 parts oatmeal, 30 parts powdered skim milk, 8 parts cod-liver oil, 1 part salt), but I find his collection of mouse lore from ancient civilizations fascinating.

Keeler, C.E. (1931). The Laboratory Mouse. Its Origins, Heredity and Culture. Harvard University Press, Cambridge.

Welcome to The Sminthophile

2007-07-31T07:22:00.000-07:00

The word sminthophile is derived from the Greek word sminthos, meaning mouse. Clyde Keeler used the term in his speech at an awards ceremony on February 14, 1978. The ceremony celebrated inbred laboratory mice and honored the scientists who developed them and demonstrated their enormous scientific potential.¹

Clyde Keeler was one of those pioneers of mouse research. He also wrote, in 1931, the definitive history of the relationship between mice and humans.² His book describes waltzing mice in Japan, medical uses for mice and mouse products in medieval Europe, and the cult of Apollo Smintheus.

Stay tuned for more about the past, present, and future of mice.

¹ Morse, H.C., III, (Ed.) (1978) Origins of Inbred Mice. Academic Press, New York. http://www.informatics.jax.org/morsebook/

²Keeler, C.E. (1931). The Laboratory Mouse. Its Origins, Heredity and Culture. Harvard University Press, Cambridge.