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

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.