The relationship between man and mouse has had, at times, a strained history: They were vilified in the Book of Leviticus; their most feared enemy, the cat, was deified in ancient Egypt; and their English name evolved from the derogatory Sanskrit mush, meaning "to steal." (1) Over the centuries, a more amicable rapport grew between Asian and European breeders and their furry pets, prized for their exotic color and behavior. Yet only a few scientists prior to 1900 took advantage of the creatures' ubiquitous presence.
But, as the laws of Gregor Mendel were being rediscovered, the mouse began nosing its way into the scientific sphere. Before 1900, mice had been used for comparative anatomy and air quality experiments, but later, scientists chose them to test Mendel's theories because of their small size, quick breeding, and easily discernable variation. The mouse was on the way to helping reinvent biological science--and become reinvented as well.
Tens of millions of mice are bred each year to, among other things, mimic human diseases and screen the effects of drugs and toxins. Ninety percent of research mammals are mice, which are now the focus of the second biggest public genome project. The mouse has marked its place in basic research, even more in the past two decades, as new techniques emerged to genetically manipulate them to model diseases more precisely. But it's still a little early to get from mouse to cure, says Kathleen Murray, director of transgenic services at Charles River Laboratories, the world's largest supplier of these test tubes with tails.
EARLY HISTORY MAKERS: A BREED APART A farm in Granby, Mass. is an ancestral epicenter for hundreds of strains used today. Retired schoolteacher Abbie Lathrop bred mice that were derived from stocks traded among Chinese, Japanese, and European fanciers. These "fancy" rodents, prized for their exotic fur colors, caught the attention of Harvard biologist William Castle. In 1901, he saw the potential in using these easily discernable variations to test Mendel's theories. Though similar research was happening in France and England, Castle's work garnered him the title of great-grandfather of mammalian genetics. (1) As genetic variants dwindled, however, so did some researchers' interest. The pot needed stirring, and in 1909, the ladle holder was Harvard undergrad Clarence Cook Little.
Wanting to transplant and study tumors in mice, Little recognized the need for a more homogenous breed. He inbred brothers and sisters past 20 generations to create animals that would not reject tumor grafts. Despite criticism from people like Castle, who felt that the compromised health of consanguineous couplings would reduce their value, and others who morally opposed forced incest, Little went ahead. (2) His end result, DBA, was bred to express recessive characteristics--dilute, brown, and non-agouti. The first inbred strain, DBA is regaled by...
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