Model Organisms

Because rats and mice are mammals, they share more genes with humans than some other popular model organisms and can be used to study common mammalian physiology as well as human disease. The mouse is used extensively for biomedical research, and was the first mammal to have its genome completely sequenced. In the early 1900s, cancer researchers at Cold Spring Harbor developed the mouse strain (called C57-Black) whose genome was sequenced. Today, dozens of mouse variants are commercially available for studying human disease from places like Jackson Laboratory in Bar Harbor, Maine.

Compared with mammals such as dogs and apes, rodents are small and inexpensive to raise, have a short generation time, and are relatively easy to work with.

A scientist and her ratsOn comparing the genomes of humans, mice, and other organisms:

"Every scientist would love to take a genome and figure out what every single letter of the genome is doing. And the way you could do that in theory is experimentally change each letter. You could do it in cell culture and see what effect that had . . . but my goodness, what a tedious, expensive, and slow process.

"It turns out, that’s what evolution does everyday. Every morning, evolution makes mutations here and there, new organisms arise in a species with a few changes here, a few changes there, and natural selection decides whether this was a good idea or not, whether you’ve disrupted an essential function or perhaps created a new function that’s valuable.

"If we look at the human sequence and the mouse sequence, which descend from a common ancestor maybe seventy-five million years ago, and ask what’s been preserved, what’s been preserved, better than chance, must be the things that matter. You can regard genomes as the laboratory notebook of evolution over seventy-five million years. We’ve got records, in the form of DNA, of all the evolutionary experiments on this planet. What we have to do is become really thoughtful, sensitive readers of [those records]."

Eric Lander, Director, Whitehead Institute's Center for Genome Research

Rat in experimentOn rats as model organisms for studying the brain:
"Rats are good model organisms because, as mammals, they’re close to humans but not too close. There's a compromise between what you can do ethically in an organism and the organism being evolutionarily close to humans. You cannot study decisions in a worm and you cannot ask a person to open up his or her head and examine the brain with electrophysiological tools. The kinds of questions we are asking are currently studied mainly in monkeys, but we believe rats will be just as useful. So we get a level of analysis that is only possible in humans very rarely, such as the case of a patient having surgery for epilepsy. In humans, we usually get a much coarser view of the brain than we get with rats."

On comparing rats and humans:
"Our ignorance of the neurological basis of human behavior is extreme. If someone is diagnosed with schizophrenia, they're treated with a drug whose mechanism of action we barely understand. Although in some cases it makes the person a little bit better, we really don't know why mechanistically that happens. Human decision-making and human behavior seem very far from rat behavior, but these drugs that we use to treat schizophrenia or depression or attention deficit disorder mostly are acting on neurotransmitter systems that are, as far as we understand them, the same in rats and humans."

Zachary Mainen, Research biologist, Cold Spring Harbor Laboratory at MIT



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