Melanocortin-3 Receptor Knockout Mice
OHSU # 0502
The central melanocortin system is critical for the long term regulation of energy homeostasis. Null mutations of the melanocortin-4 receptor (MC4-R) are associated with hyperphagia, obesity, and accelerated longitudinal growth in mice and humans. To assess the role of the melanocortin-3 receptor (MC3-R) in energy homeostasis, the mc3r coding sequence was deleted from the mouse genome. In contrast to the MC4-R knockout, which exhibits increased food intake, increased somatic growth, and defects in metabolism, mc3r-/-mice exhibit an exclusively metabolic syndrome. Homozygous null mc3r mice, while not significantly overweight, exhibit an approximately 50% to 60% increase in adipose mass. Mc3r-/- mice also exhibit an unusual increase in respiratory quotient when transferred onto high fat chow, suggesting a reduced ratio of fat/carbohydrate oxidation. Furthermore, male mc3r-/- mice also exhibit an approximately 50% reduction in locomotory behavior on the running wheel, suggesting reduced energy expenditure.
No other MC3-R knockout mouse model is known to exist.
This model would be useful for studying melanocortin signaling, and as a screening tool for MC3-R agonists and antagonists effective for metabolic regulation, obesity, energy homeostasis, insulin secretion and the development of anti-inflammation therapeutics.
Roger Cone earned his Ph.D. in Biology from the Massachusetts Institute of Technology in 1985. He received his B.A. in Biochemistry from Princeton University. Starting in 1985, Cone was a fellow at the Cold Spring Harbor Laboratory. In 1988, he became an assistant professor in the Division of Molecular Medicine at the New England Medical Center, where he remained until he accepted his appointment to the Vollum in 1990. Cone moved to Vanderbilt University in 2008 and is the Chair of the Department of Molecular Physiology and Biophysics.
Endocrinology. 2000 Sep;141(9):3518-21
Breeding pairs of this mouse strain are available for non-exclusive licensing.
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Technology Development Manager