Since Chawnshang Chang, Ph.D., cloned the gene for testicular orphan receptor 4 (TR4) 10 years ago, he and other scientists have tried to learn its function scientists call it an "orphan" receptor because they don't know what protein links up with it. So a team led by Chang, director of George Whipple Laboratory for Cancer Research at the University of Rochester Medical Center, knocked out the gene in mice, then watched what happened.
They found that many of the mice died before birth. Those that lived are markedly smaller than their normal counterparts: They're born far smaller and then make up some of the difference as they grow, but generally they are about 20 to 30 percent smaller by the time they reach adulthood. The miniature mice are not as fertile as normal mice, having only about half the offspring as other mice.
Most visibly, the females have very bad parenting skills: They don't build nests, nurse their young, or tend to their offspring, which die within a day or two as a result.
"Basically, we observed mothers that don't care for their pups," says post-doctoral associate Loretta Collins, Ph.D., who did much of the work along with Yi-Fen Lee, Ph.D., assistant professor of urology. "A normal mouse will gather its offspring and crouch over them and take care of them, but these "knockout" mice just left their pups scattered about the cage.
"Our plans to further characterize behavior and gene expression in these animals will help us identify the target genes that are normally controlled by TR4 and contribute to regulation of specific behaviors," she adds.