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Previous Article | Next Article
The Journal of Neuroscience, January 15, 2003, 23(2):539-549
Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice
Eugene P. Brandon1, *, Weichun Lin2, *, Kevin A. D'Amour1, Donald P. Pizzo3, Bertha Dominguez2, Yoshie Sugiura4, Silke Thode1, Chien-Ping Ko4, Leon J. Thal3, Fred H. Gage1, and Kuo-Fen Lee2 1 Laboratory of Genetics and 2 Peptide Biology Laboratories, The Salk Institute for Biological Studies, La Jolla, California 92037, 3 Department of Neurosciences, School of Medicine, University of California at San Diego, La Jolla, California 92037, and 4 Neurobiology Section, Department of Biological Sciences, University of Southern California, Los Angeles, California 90089
In this study we examined the developmental roles of acetylcholine (ACh) by establishing and analyzing mice lacking choline acetyltransferase (ChAT), the biosynthetic enzyme for ACh. As predicted, ChAT-deficient embryos lack both spontaneous and nerve-evoked postsynaptic potentials in muscle and die at birth. In mutant embryos, abnormally increased nerve branching occurs on contact with muscle, and hyperinnervation continues throughout subsequent prenatal development. Postsynaptically, ACh receptor clusters are markedly increased in number and occupy a broader muscle territory in the mutants. Concomitantly, the mutants have significantly more motor neurons than normal. At an ultrastructural level, nerve terminals are smaller in mutant neuromuscular junctions, and they make fewer synaptic contacts to the postsynaptic muscle membrane, although all of the typical synaptic components are present in the mutant. These results indicate that ChAT is uniquely essential for the patterning and formation of mammalian neuromuscular synapses.
Key words: choline acetyltransferase; acetylcholine; neural development; mice; neuromuscular; gene knock-out
* E.P.B. and W.L. contributed equally to this study.
Copyright © 2003 Society for Neuroscience 0270-6474/03/232539-11$05.00/0
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