M1-M3 muscarinic acetylcholine receptor-deficient mice: novel phenotypes.
The five muscarinic acetylcholine receptors (M1-M5 mAChRs) mediate a very large number of important physiological functions (Caulfield, 1993; Caulfield and Birdsall, 1998; Wess, 2004). Because of the lack of small molecule ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues or cell types express two or more mAChR subtypes, identification of the physiological and pathophysiological roles of the individual mAChR subtypes has proved to be a challenging task. To overcome these difficulties, we recently generated mutant mouse lines deficient in each of the five mAChR genes (M1R-/- mice, M2R-/- mice, M3R-/- mice, etc. [Wess, 2004]). Phenotyping studies showed that each of the five mutant mouse lines displayed characteristic physiological, pharmacological, behavioral, biochemical, or neurochemical deficits (Wess, 2004). This chapter summarizes recent findings dealing with the importance of the M2mAChR for cognitive processes and the roles of the M1 and M3 mAChRs in mediating stimulation of glandular secretion.
Gautam
Dinesh
D
Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Duttaroy
Alokesh
A
Cui
Yinghong
Y
Han
Sung-Jun
SJ
Deng
Chuxia
C
Seeger
Thomas
T
Alzheimer
Christian
C
Wess
Jürgen
J
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003071:Cognition / Q000502:physiology*; D006728:Hormones / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D043643:Receptor, Muscarinic M1 / Q000172:deficiency* / Q000235:genetics; D043585:Receptor, Muscarinic M2 / Q000172:deficiency* / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000172:deficiency* / Q000235:genetics
D006728:Hormones; D007328:Insulin; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D002217:Carbachol