Fifth obesity gene found in mice.

Investigators have rapidly been uncovering individual genes that, when mutated, produce obese mice. They first identified the genes at fault in the mouse strains known as yellow, fat, obese, and diabetes. Now a fifth mouse strain, tubby, is due its 15 minutes of fame: Two separate research groups have reported the discovery of a mutated gene in the hefty rodents. Both teams pinpointed the same gene, according to their reports in the April 11 Nature and the April 19 Cell. The Nature report comes from a collaboration between Jackson Laboratory in Bar Harbor, Maine, and Sequana Therapeutics in La Jolla, Calif.

"We had been working on this gene for two and a half years," says Jackson Laboratory's Patsy M. Nishina, who headed the collaboration. Though Nishina's team published its findings first, it may have lost the commercial race to Millennium Pharmaceuticals of Cambridge, Mass. The biotech firm found the tubby gene and filed patents on it last summer, says a company spokesperson, but it delayed publishing to preserve a research advantage. The tubby mouse has interested researchers because it models the course of human obesity more closely than do the obese and diabetes strains, in which the rodents eat ravenously from birth. Tubby mice don't overeat; they gain weight slowly, as they age. Like people with diabetes, the mice have troubles with their insulin metabolism. Moreover, the rodents lose their sight and hearing at an early age.

Both research groups found that a small mutation in the tubby gene altered the protein it codes for, replacing a normal sequence of 44 amino acids with a string of 20 amino acids. The tubby gene is most active in the brain, eyes, and testes of mice, but investigators do not yet know its protein's function or how the mutation causes the problems in tubby mice.

Researchers have found that humans, as well as fruit flies and worms, possess a gene similar to the tubby gene and plan to examine whether it's mutated in obese people.