TY - JOUR
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, T.
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.
N1 - Funding Information:
This work was supported by the JSPS Research Fellowship Program (M. Y.) and by NIH Grants HL-38901, HL-39050, HL-62984, and NS-24621 (K. G. L , F. M. F.). We also thank all individuals who are not listed as coauthors but who contributed to various aspects of the work summarized in this article.
PY - 2003
Y1 - 2003
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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U2 - 10.1080/10606820308262
DO - 10.1080/10606820308262
M3 - Review article
C2 - 12893539
AN - SCOPUS:0041912472
SN - 1060-6823
VL - 9
SP - 279
EP - 290
JO - Receptors and Channels
JF - Receptors and Channels
IS - 4
ER -