Methods and Compositions for Analysis of M3 Muscarinic Acetylcholine Receptors
Description of Invention:
This invention discloses transgenic mice that have the M3 Muscarinic Acetylcholine Receptor deleted by gene knockout technology. These mice were developed in order to better understand the physiological relevance of the M3 receptor. Unexpectedly, these knockout mice have a phenotype that includes significant reduction in food intake, weight loss, peripheral fat deposits, as well as very low serum leptin and insulin levels. It was also found that the M3 receptor is highly expressed in the hypothalamus, a region of the brain known to be critically involved in regulation of food uptake. The mice also show physiological changes (increased levels of hypothalmic agouti-related peptide mRNA and decreased expression of propiomelanocortin mRNA) consistent with those observed in fasted animals. However, the knockout mice also have changes (reduced levels of melanin concentrating hypothalmic mRNA) inconsistent with fasted animals. These data point to the existence of a novel cholinergic pathway involving M3 cholinergic receptor mediated stimulation of food intake. This technology strongly suggests that agents which can specifically and selectively act as antagonists of the M3 subtype receptors may be useful in the treatment of obesity.
Patent Status:
DHHS Reference No. E-291-2000/0 -- Research Materials
Portfolios: Internal Medicine Gene Based Therapies Central Nervous System
Central Nervous System -Research Materials-Transgenics Central Nervous System -Research Materials Gene Based Therapies -Diagnostics Gene Based Therapies -Research Materials Internal Medicine-Research Materials
For Additional Information Please Contact: Charlene A. Sydnor Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: 301/435-4689
Email: sydnorc@mail.nih.gov
Fax: 301/402-0220
