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!
A new technique isolates neuronal activity during memory consolidation
22.06.2017 | Spanish National Research Council (CSIC)
CWRU researchers find a chemical solution to shrink digital data storage
22.06.2017 | Case Western Reserve University
Heatwaves in the Arctic, longer periods of vegetation in Europe, severe floods in West Africa – starting in 2021, scientists want to explore the emissions of the greenhouse gas methane with the German-French satellite MERLIN. This is made possible by a new robust laser system of the Fraunhofer Institute for Laser Technology ILT in Aachen, which achieves unprecedented measurement accuracy.
Methane is primarily the result of the decomposition of organic matter. The gas has a 25 times greater warming potential than carbon dioxide, but is not as...
Hydrogen is regarded as the energy source of the future: It is produced with solar power and can be used to generate heat and electricity in fuel cells. Empa researchers have now succeeded in decoding the movement of hydrogen ions in crystals – a key step towards more efficient energy conversion in the hydrogen industry of tomorrow.
As charge carriers, electrons and ions play the leading role in electrochemical energy storage devices and converters such as batteries and fuel cells. Proton...
Scientists from the Excellence Cluster Universe at the Ludwig-Maximilians-Universität Munich have establised "Cosmowebportal", a unique data centre for cosmological simulations located at the Leibniz Supercomputing Centre (LRZ) of the Bavarian Academy of Sciences. The complete results of a series of large hydrodynamical cosmological simulations are available, with data volumes typically exceeding several hundred terabytes. Scientists worldwide can interactively explore these complex simulations via a web interface and directly access the results.
With current telescopes, scientists can observe our Universe’s galaxies and galaxy clusters and their distribution along an invisible cosmic web. From the...
Temperature measurements possible even on the smallest scale / Molecular ruby for use in material sciences, biology, and medicine
Chemists at Johannes Gutenberg University Mainz (JGU) in cooperation with researchers of the German Federal Institute for Materials Research and Testing (BAM)...
Germany counts high-precision manufacturing processes among its advantages as a location. It’s not just the aerospace and automotive industries that require almost waste-free, high-precision manufacturing to provide an efficient way of testing the shape and orientation tolerances of products. Since current inline measurement technology not yet provides the required accuracy, the Fraunhofer Institute for Laser Technology ILT is collaborating with four renowned industry partners in the INSPIRE project to develop inline sensors with a new accuracy class. Funded by the German Federal Ministry of Education and Research (BMBF), the project is scheduled to run until the end of 2019.
New Manufacturing Technologies for New Products
19.06.2017 | Event News
13.06.2017 | Event News
13.06.2017 | Event News
22.06.2017 | Life Sciences
22.06.2017 | Materials Sciences
22.06.2017 | Materials Sciences