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M3 Muscarinic Receptor Knockout Mice (Chrm3 tm1Jwe) for the Study of Obesity and Other Metabolic Disorders

Posted May 15 2012 8:00pm

Description of Invention:
The five Muscarinic Acetylcholine (ACh) receptors are G-protein coupled receptors (M1R-M5R). M3 muscarinic ACh receptors are present in the central nervous system and the periphery.

M3R knockout mice are viable and fertile, and have no major morphological abnormalities. They have a lean phenotype due to a combination of reduced caloric intake and increased energy expenditure. Because of their lean phenotype, M3R knockout mice have improved glucose tolerance and increased insulin sensitivity. Pharmacological blockade of central M3Rs may be a novel strategy for the treatment of obesity and associated metabolic disorders.

In the airway, vagally-mediated bronchoconstriction responses were abolished in M3R knockout mice in vivo, suggesting that M3R antagonists may be useful in the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Studies with M3R knockout mice also have shown that the M3R is the major muscarinic receptor mediating ACh-induced glandular secretion from exocrine and endocrine glands, including the secretion of insulin from pancreatic beta cells.

Applications:
Animal model to study COPD and metabolism.

Advantages:
M3R knockout mice are viable and fertile, and have no major morphological abnormalities.

Development Status:
Pre-clinical

Inventors:
Jurgen Wess (NIDDK)


Patent Status:
HHS, Reference No. E-346-2004/2

Research Tool — Patent protection is not being pursued for this technology.

Related Technologies:

HHS Reference No. E-346-2004/0 — M1 Muscarinic receptor KO (Chrm1tm1Jwe) Mice
HHS Reference No. E-346-2004/1 — M2 Muscarinic receptor KO (Chrm2 tm1Jwe) Mice

Relevant Publication:
  1. Yamada M, et al. [ PMID 11242080 ]



For Licensing Information Please Contact:
Admin. Licensing Spec-GenMed
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: rodrigr@mail.nih.gov
Phone: 301-496-7057
Fax: 301-402-0220


Ref No: 2440

Updated: 05/2012

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