Building a better mouse

As NIH scientists rush towards a similar goal—a complete library of knockout mice—it is unclear whether Xu’s mice will become the favored research animals or simply one of several options for scientists. But if it works, Xu’s massive experiment could serve as a demonstration project for how to catalog an entire genome quickly. He’s already shown that a similar transposon technology can be used to create mutant rats, and he believes it could work in other mammal species that may be preferable for some kinds of research. Moreover, Xu says his mice are likely to be less expensive to use because his method creates live breeding pairs. The NIH library will provide modified stem cells that are many complex steps away from living research animals, because scientists must transfer them into mouse embryos that they then breed for several generations.

Research has also shown that different mutant technologies can yield subtly different effects, and Xu’s mice may be favored by certain scientists. “Our work is complementary,” says Kent Lloyd, a veterinarian and research physiologist at the University of California–Davis who is working on the NIH knockout project.

Xu is also carving out his own project in the mouse genome. He knows that most of the mice he creates will benefit other researchers, but he’s taken an interest in a few mutants they’ve already uncovered. One particularly promising mutant has trouble absorbing nutrients in its digestive system. It is born with chronic diarrhea and ultimately dies after suffering many of the same symptoms seen in starving children. Xu thinks the mouse could serve a double value. By determining how to improve the efficiency of its digestive system, Xu hopes he can help develop treatments to mitigate starvation in parts of the world where food is scarce. He also hopes the mouse’s inefficient digestive system will help him find ways for humans who eat junk food and live sedentary lives to avoid the ravages of diabetes and heart disease. It’s a very American question for a Chinese mouse.