Tuesday, December 18, 2007

Waxing Political

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.

Saturday, December 8, 2007

Mice on Drugs!

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?

Saturday, November 10, 2007

The Energizer Mouse

video

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.

Friday, October 19, 2007

EEK!


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...

Thursday, October 18, 2007

How to knock out (or knock in) a gene

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.

Tuesday, October 9, 2007

Hail the Nobel Mouse!

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!

Wednesday, September 12, 2007

Aspergian Mice

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



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.

Wednesday, August 29, 2007

Buff Mice

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

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

Let me know if you can get it to work.

Tuesday, August 28, 2007

The accidental compulsive

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 .

Monday, August 13, 2007

Spinning Mice

I found this cartoon from 1935.

video

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.

Tuesday, August 7, 2007

The old song and dance

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.

Thursday, August 2, 2007

Three ways to make a schizophrenic mouse

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


Wednesday, August 1, 2007

Fearless Mice

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:

Bild:Psalmopoeus cambridgei 7 FH.jpg

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.

Tuesday, July 31, 2007

More Déjà Vu...Autism Cured in Mice!


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?

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?


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 you haven’t.

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


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



1
Keeler, 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

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!

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

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

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.