Next time you take your medicine, consider that mice likely helped in testing it.

The structure of human and mouse DNA is about 96 percent similar, which makes mice excellent subjects for testing products that could be used on humans. As research has progressed, however, a problem arose within the mice population.

There were very few strains of mice bred for testing, which led to a severe lack of genetic diversity in lab mice. Despite the similarities in DNA structure, the diversity of the mouse population did not match the diversity of the human population, and lab test results in mice could not be safely extrapolated to humans.

In 2001, a program called Collaborative Cross sought to fix this problem. David Threadgill, head of the Genetics Department, works with this group to find ways to diversify lab mouse populations.

"When we started this project, at least a third or half of the mouse genome had no diversity in it, so there were blind spots within the genome, and you couldn't interrogate functions of those parts," Threadgill said.

Threadgill and his colleagues randomly bred eight strains of lab and wild mice, creating a library of test mouse strains with sufficient diversity to mirror the human population.

"We use mice as a surrogate for you, to investigate the causation of human disease," Threadgill said.

Collaborative Cross now has about 1,600 strains of mice, housed and curated at a facility in Chapel Hill. Ten representatives of each strain are kept in the facility's 16,000 cages and are made available to researchers around the world. The mice of Collaborative Cross are currently used in various research projects. From cancer research to infertility studies, these mice of a diverse genetic background enable researchers to investigate the genetic basis of human disease more thoroughly.

Human cell division may mutate into the uncontrolled division of cells, resulting in the development of a cancerous tumor, but researchers can now investigate the causative factors in an expendable mouse population that more closely mirrors the human genome. Because the carriers of these genes, the mice, reproduce very quickly, complete investigations of the behavior and function of genes in relation to the disease in question are possible.

Though Collaborative Cross doesn't just offer mice for direct testing, it also maintains a massive library of genes. Each individual bred through the project has its DNA catalogued in an online resource available to the public. This genome browser is a critical aspect of the project.

It is important in consolidating the work of Collaborative Cross, and offers an excellent reference for any scientist doing work with test mice, according to Threadgill. For example, some diseases are caused by unfavorable combinations of specific genes in an organism's DNA.

"What these mice are telling us is that a lot of human diseases are coming about because of genetic disruption of normal feedback systems," Threadgill said. "There are unique combinations of genetic variation that just don't function well together."

With a resource like the mouse genome library, these unfavorable polymorphisms in genes can be identified, isolated and studied through population analysis.

In the future, Collaborative Cross plans to expand their operation, with new distribution centers around the world and more strains of mice. Being able to perform large scale studies on diverse populations will be even more important as we develop a better understanding of the genetic basis of disease.

For complicated problems, complicated models are needed. According to Threadgill, that's just what Collaborative Cross is developing. 

Link:
Researchers diversify lab mouse gene pool