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, Tsuyoshi Miyakawa, F. P. Bymaster, L. McKinzie, C. C. Felder, K. G. Lamping, F. M. Faraci, C. Deng, M. Yamada

Research output: Contribution to journalReview article

78 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)279-290
Number of pages12
JournalReceptors and Channels
Volume9
Issue number4
DOIs
Publication statusPublished - 15-09-2003
Externally publishedYes

Fingerprint

Muscarinic M5 Receptors
Muscarinic M1 Receptors
Muscarinic Receptors
Knockout Mice
Cholinergic Agents
Genes
Neurology
Animals
Wild Animals
Gene Targeting
Peripheral Nervous System
Tissue
Ligands
Central Nervous System
Pharmaceutical Preparations
Pharmacology
Technology
Mutation

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Wess, J. ; Duttaroy, A. ; Zhang, W. ; Gomeza, J. ; Cui, Y. ; Miyakawa, Tsuyoshi ; Bymaster, F. P. ; McKinzie, L. ; Felder, C. C. ; Lamping, K. G. ; Faraci, F. M. ; Deng, C. ; Yamada, M. / M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system. In: Receptors and Channels. 2003 ; Vol. 9, No. 4. pp. 279-290.
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abstract = "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.",
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Wess, J, Duttaroy, A, Zhang, W, Gomeza, J, Cui, Y, Miyakawa, T, Bymaster, FP, McKinzie, L, Felder, CC, Lamping, KG, Faraci, FM, Deng, C & Yamada, M 2003, 'M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system', Receptors and Channels, vol. 9, no. 4, pp. 279-290. https://doi.org/10.1080/10606820308262

M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system. / Wess, J.; Duttaroy, A.; Zhang, W.; Gomeza, J.; Cui, Y.; Miyakawa, Tsuyoshi; Bymaster, F. P.; McKinzie, L.; Felder, C. C.; Lamping, K. G.; Faraci, F. M.; Deng, C.; Yamada, M.

In: Receptors and Channels, Vol. 9, No. 4, 15.09.2003, p. 279-290.

Research output: Contribution to journalReview article

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T1 - M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system

AU - Wess, J.

AU - Duttaroy, A.

AU - Zhang, W.

AU - Gomeza, J.

AU - Cui, Y.

AU - Miyakawa, Tsuyoshi

AU - Bymaster, F. P.

AU - McKinzie, L.

AU - Felder, C. C.

AU - Lamping, K. G.

AU - Faraci, F. M.

AU - Deng, C.

AU - Yamada, M.

PY - 2003/9/15

Y1 - 2003/9/15

N2 - 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.

AB - 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.

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