Novel muscarinic receptor mutant mouse models

Abstract

Muscarinic acetylcholine (ACh) receptors (mAChRs; M₁-M₅) regulate the activity of an extraordinarily large number of important physiological processes. During the past 10-15 years, studies with whole-body M₁-M₅ mAChR knockout mice have provided many new insights into the physiological and pathophysiological roles of the individual mAChR subtypes. This review will focus on the characterization of a novel generation of mAChR mutant mice, including mice in which distinct mAChR genes have been excised in a tissue- or cell type-specific fashion, various transgenic mouse lines that overexpress wild-type or different mutant M₃ mAChRs in certain tissues or cells only, as well as a novel M₃ mAChR knockin mouse strain deficient in agonist-induced M₃ mAChR phosphorylation. Phenotypic analysis of these new animal models has greatly advanced our understanding of the physiological roles of the various mAChR subtypes and has identified potential targets for the treatment of type 2 diabetes, schizophrenia, Parkinson's disease, drug addiction, cognitive disorders, and several other pathophysiological conditions.