Friday, June 1, 2007

Mouse Models

No one knows with much certainty just how many mice are consumed annually in American labs. Estimates of 20 to 30 million are common. But creating today's exotic strains -- with more or less precisely defined genetics -- can entail killing twenty or more mice for each one that meets a scientist's demands. These by-products of the industry do not rate even a tally mark.

The use of mice and every other "model" species is based on the notion that mice and humans are essentially the same when it comes to basic biology. The claim is that if we can learn how a drug is metabolized in the liver of a mouse, for instance, we can assume that it will be somewhat similarly metabolized in a human.

Strong theoretical arguments explain why these assumptions turn out to be false more often than not (nearly always in fact), but the animal research community chooses to ignore the history of failure and continues to hurt and consume these little beasts in ever-growing numbers.

In the case of mouse livers and human livers, a recent study by researchers at MIT explains why mice fail so uniformily as good predictive models. An MIT press release explains:
The researchers and their colleagues had previously worked out many aspects of gene regulation in the human liver, which is one reason the researchers chose to study the [mouse] liver. In the current study they compared 4,000 human genes with nearly identical counterparts, known as homologous genes, from mouse liver cells.

Given the similarity between the two species' DNA sequences, the researchers expected that transcription factors would bind to the same sites in most pairs of homologous genes. To their surprise, they found that most of the binding sites--between 41 percent and 89 percent, depending on the transcription factor--were in different locations in humans and mice.

"The number of genes with the identical regulation in both species was very, very small," [Ernest] Fraenkel said.

Before they began, the researchers expected to see some differences in gene regulation between mice and humans, because the human liver has evolved to process cooked food, said Fraenkel. However, the magnitude of change was much higher than they anticipated.
Not surprisingly, they now say that it is the absence of similarity that makes mice valuable tools.

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