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, a new study by UT Southwestern Medical Center researchers suggests.
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."
"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," said Nobel Laureate Dr. Beutler, Director of the Center for the Genetics of Host Defense. "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.
"Whereas many heritable obesity phenotypes are known, lean phenotypes are comparatively uncommon. Yet they can reveal critical checkpoints regulating energy balance," the researchers said.
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, appearing in the Proceedings of the National Academy of Sciences, may be explained by the apparent involvement of Sterile alpha motif domain containing protein 4 (Samd4) in a specific cell signaling pathway, which tell cells how to interact, called mTORC1. mTORC1 is a master regulatory complex that governs aspects of energy balance, including metabolism, development, autophagy (cell recycling), and other processes in cells.
Dr. Bruce A. Beutler shared the 2011 Nobel Prize in Physiology or Medicine with two other scientists for their discoveries related to activation of the immune system.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution's faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
Russell Rian | Eurek Alert!
Faster detection of pathogens in the lungs
24.06.2016 | Universität Zürich
How yeast cells regulate their fat balance
23.06.2016 | Goethe-Universität Frankfurt am Main
Physicists in Innsbruck have realized the first quantum simulation of lattice gauge theories, building a bridge between high-energy theory and atomic physics. In the journal Nature, Rainer Blatt‘s and Peter Zoller’s research teams describe how they simulated the creation of elementary particle pairs out of the vacuum by using a quantum computer.
Elementary particles are the fundamental buildings blocks of matter, and their properties are described by the Standard Model of particle physics. The...
A year and a half on the outer wall of the International Space Station ISS in altitude of 400 kilometers is a real challenge. Whether a primordial bacterium...
Researchers at Case Western Reserve University have developed a way to swiftly and precisely control electron spins at room temperature.
A physics experiment performed at the National Institute of Standards and Technology (NIST) has enhanced scientists' understanding of how free neutrons decay...
Chemically the same, graphite and diamonds are as physically distinct as two minerals can be, one opaque and soft, the other translucent and hard. What makes...
09.06.2016 | Event News
24.05.2016 | Event News
20.05.2016 | Event News
24.06.2016 | Materials Sciences
24.06.2016 | Physics and Astronomy
24.06.2016 | Physics and Astronomy