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What is a laboratory mouse?

Gary Churchill, Ph.D.

What, genetically, are laboratory mice? It's a very important issue. A lack of genetic diversity limits the potential for new research discoveries and makes it much more difficult to translate findings in mouse models to human medicine.

Did the mice originally come from several different wild and domestic mouse species? Or are they almost entirely descended from the domesticated "fancy" mice popular in the late 1800s? It seems like a basic question, but until recently researchers didn't know for sure. And for Jackson Laboratory Professor Gary Churchill, Ph.D., not knowing was unacceptable. "It's embarrassing," he says, "to have such a highly used model organism and not really understand what its relationship is to the wild."

Now Churchill and Fernando Pardo-Manuel de Villena, Ph.D., of the University of North Carolina, Chapel Hill, have led an international effort to provide a definitive answer. In a paper published in Nature Genetics, they conclude that most laboratory mice represent limited genetic diversity and are derived almost entirely from mice kept and traded as pets in the 19th century.

Churchill and Pardo-Manuel de Villena have been working for almost a decade to make laboratory mice more effective for translational research. The Collaborative Cross and Diversity Outbred mouse population projects have included wild-derived strains to greatly increase genetic diversity and more accurately model human genetics. These mice provide 45 million sites of genetic variation, nearly four times more than can be found in standard laboratory mouse strains. "All these variants give us a lot more handles into understanding the genome," says Churchill.

Yang et al. 2011. Subspecific origin and haplotype diversity in the laboratory mouse. Nature Genetics 43:648-655.