M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system

J. Wess, A. Duttaroy, W. Zhang, J. Gomeza, Y. Cui, T. Miyakawa, F. P. Bymaster, L. McKinzie, C. C. Felder, K. G. Lamping, F. M. Faraci, C. Deng, M. Yamada

研究成果: Review article査読

82 被引用数 (Scopus)

抄録

A large body of evidence indicates that muscarinic acetylcholine receptors (mAChRs) play critical roles in regulating the activity of many important functions of the central and peripheral nervous systems. However, identification of the physiological and pathophysiological roles of the individual mAChR subtypes (M1-M5) has proven a difficult task, primarily due to the lack of ligands endowed with a high degree of receptor subtype selectivity and the fact that most tissues and organs express multiple mAChRs. To circumvent these difficulties, we used gene targeting technology to generate mutant mouse lines containing inactivating mutations of the M1-M5 mAChR genes. The different mAChR mutant mice and the corresponding wild-type control animals were subjected to a battery of physiological, pharmacological, behavioral, biochemical, and neurochemical tests. The M1-M5 mAChR mutant mice were viable and reproduced normally. However, each mutant line displayed specific functional deficits, suggesting that each mAChR subtype mediates distinct physiological functions. These results should offer new perspectives for the rational development of novel muscarinic drugs.

本文言語English
ページ(範囲)279-290
ページ数12
ジャーナルReceptors and Channels
9
4
DOI
出版ステータスPublished - 2003
外部発表はい

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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