Should the Mouse Model be Used to Study Human Diseases?

The mouse is a common model used in research as a way of studying human biology and diseases, but a new study questions whether this is an accurate approach considering some stark differences - aside from many similarities - between the two species.

The results were published in four papers in the journal Nature.

By examining the genetic and biochemical programs involved in regulating mouse and human genomes, an international group of researchers has found that for the most part the systems involved in controlling gene activity have many similarities between mice and humans. These systems include the immune system, metabolism, and stress response, and have been conserved through evolution.

"We have known that the mouse was mostly a good model for humans. We found that many processes and pathways are conserved from mouse to human. This allows us to study human disease by studying those aspects of mouse biology that reflect human biology," Bing Ren, co-senior author on the main Nature study, said in a statement.

But while, in general, these rodents and humans share the same basic genetic machinery, the differences are in the details. For example, for the mouse immune system, certain gene activity varies between mice and humans, as previous research has indicated. Researchers then subsequently identified some genes found in mice that lack a counterpart in humans.

"That may be a result of mouse and human adaptation to their respective environments," Ren explained.

Mice and humans may share 70 percent of the same protein-coding gene sequences, but that's actually just 1.5 percent of their overall genomes, showing that there is plenty of room for differences between the two.

Two companion studies further illustrated utter differences, specifically pertaining to 1.3 million genome locations called DNase 1 hypersensitivity, which identify regulatory DNA. By comparing 45 mouse cell and tissue types with those in humans, they found that about 35 percent of these elements were shared by mice and humans, however they were active in dissimilar types of cells.

"Mouse and human genomes to have a common language in regulation, but there is a tremendous amount of flexibility in evolution," said researcher John Stamatoyannopoulos from the University of Washington, Seattle, senior author of one the studies. "For example, an element active in the mouse liver might be repurposed to be active in the brain in the human."

With these differences in mind, scientists can better determine when it's appropriate to use lab mice to study human biology and disease, as well as understand more clearly some of the mouse model's limitations.

The findings were reported by the mouse ENCODE Consortium and described in the main Nature study, as well as in the papers "Principles of regulatory information conservation between mouse and human," "A comparative encyclopedia of DNA elements in the mouse genome," and "Conservation of trans-acting circuitry during mammalian regulatory evolution."