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!
Rapid adaptation to a changing environment
28.04.2016 | Christian-Albrechts-Universität zu Kiel
Tiny microscopes reveal hidden role of nervous system cells
28.04.2016 | Salk Institute
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences (CAS). This work is about avoiding costly and unstable fullerenes.
Polymer solar cells can be even cheaper and more reliable thanks to a breakthrough by scientists at Linköping University and the Chinese Academy of Sciences...
As one of the leading R&D partners in the development of surface technologies and organic electronics, the Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP will be exhibiting its recent achievements in vacuum coating of ultra-thin glass at SVC TechCon 2016 (Booth 846), taking place in Indianapolis / USA from May 9 – 13.
Fraunhofer FEP is an experienced partner for technological developments, known for testing the limits of new materials and for optimization of those materials...
Liquid water is a very good heat storage medium – anyone with a Thermos bottle knows that. However, as soon as water boils or freezes, its storage capacity drops precipitously. Physicists at the University of Bonn have now observed very similar behavior in a gas of light particles. Their findings can be used, for example, to produce ultra-precise thermometers. The work appears in the prestigious technical journal "Nature Communications".
Water vapor becomes liquid under 100 degrees Celsius – it condenses. Physicists speak of a phase transition. In this process, certain thermodynamic...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
28.04.2016 | Physics and Astronomy
28.04.2016 | Materials Sciences
28.04.2016 | Life Sciences