How the 'Mouse Man' Changed Medical Research

In fact, the lab mouse might have got off to a much earlier start if Gregor Mendel - the father of genetics - hadn't been thwarted by his bishop. In the 1850s, Mendel began his investigation of inheritance by studying coat-colour traits in mice. But he was a monk and his bishop decreed that a monastery was no place to experiment with copulating mice. Mendel switched to a study of peas.

Nor were biologists the only people to experiment with mice. Breeders of fancy mice had tinkered with mouse genes for centuries. Seventeenth-century illustrations show how people in Japan bred and collected unique strains, creating albinos and mice with spotted coats.

They also bred "waltzing mice" that seemed to dance, a peculiarity later discovered to be the result of an inner-ear defect.

By the 20th century, such breeders had established clubs and exhibited their prize specimens at mouse shows. As a student, Little often judged these shows at the behest of his professor William Castle, who saw it as way to scout for genetic mutants of interest to science. It was this link to mouse fanciers that ultimately led to Little's lab mouse.

More specifically, it led to one mouse fancier, retired schoolteacher Abbie Lathrop. After a failed attempt at raising poultry, Lathrop hoped to make a living from the fancy mouse craze and began to breed popular strains on her farm in Granby, Massachusetts. She soon attracted scientific customers. "I know it sounds bizarre, in terms of genetics, that people would seek out this mouse breeder on a farm in Granby," says Rader. "But she always had the best mice. She was a local celebrity."

Lathrop was also a scientist in her own right. When she noticed some of her mice suffered from skin lesions, she sent samples to her scientific clients, including Leo Loeb, a pathologist at the University of Pennsylvania. He confirmed Lathrop's suspicions that the lesions were cancerous and the pair spent the next five years publishing joint research on tumour transmission in mice.

Little, meanwhile, had recognised the potential in Lathrop's stock. Lathrop had bred many generations of brother and sister mice to create unique strains, and such relative genetic similarity would make an excellent starting point for his work. Little began his project largely because he needed to do some independent research to qualify for Harvard's doctoral programme, but he was also eager to prove one of Castle's hypotheses wrong, says Rader.

Castle believed interbreeding could never create a stable and pure genetic strain. He also doubted that the mice would remain fertile after generations of inbreeding.

Indeed, Little soon found he had taken on something of a challenge. As fancy mouse breeders had already discovered, few progeny of brother-sister matings survive. Litters are small and the young sometimes sterile. But Little eventually found a strain that flourished.

He named it dilute brown non-agouti (DBA) - dilute because it had less pigment than its wild cousins, brown as opposed to the more common black, and non-agouti because it didn't have the grizzled-looking fur of other mice.

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