'Supermodel' mouse could give new insight into diseases like diabetes, obesity

A lean "Supermodel" mouse type has revealed the potentially critical role played by a largely unknown gene that regulates metabolism, findings that could provide new insight into diseases ranging from diabetes to obesity.

The Supermodel mouse's phenotype - the physical characteristics that result from its gene makeup - include being very small in size, with an unusual body form caused by abnormal distribution of fat, said Dr. Zhe Chen, Assistant Professor of Biophysics, and Dr. Bruce Beutler, Professor of Immunology, with UT Southwestern's Center for the Genetics of Host Defense. The mouse phenotype is nicknamed "Supermodel."

Nobel Laureate Dr. Beutler, Director of the Center for the Genetics of Host Defense, said this mouse is important because it has revealed a new regulatory protein that's very important for normal metabolism, but was never known to exist before.

He said the implications of the work may be felt in diabetes and obesity research, the study of wasting in chronic disease, the study of muscle cell function, and perhaps other fields.

While at the Scripps Research Institute, Dr. Beutler developed a mouse mutagenesis program, which at UT Southwestern has become the largest and most technologically advanced in the world.

The new mouse phenotype was discovered in the lab's colony of mutant mice several years ago, but the mutation was discovered and studied entirely at UT Southwestern, in a collaboration that also involved researchers Dr. William Holland, Assistant Professor of Internal Medicine, Dr. Aktar Ali, Assistant Professor of Internal Medicine, and John Shelton, lab manager in Internal Medicine.

Together, they found that a mutation in a gene called Samd4, about which almost nothing was known in mammals, results in the abnormally lean mice, which also have diminished insulin responses to glucose and arginine.

The mice seem to waste energy, consuming excessive oxygen and producing a commensurately higher amount of CO2, despite being relatively inactive. Much of the fat in these mice seems to be abnormal, similar to "brown fat" of hibernating species.

The findings have been published in the Proceedings of the National Academy of Sciences.