TY - JOUR T1 - Aberrant Patterning of Neuromuscular Synapses in Choline Acetyltransferase-Deficient Mice JF - The Journal of Neuroscience JO - J. Neurosci. SP - 539 LP - 549 DO - 10.1523/JNEUROSCI.23-02-00539.2003 VL - 23 IS - 2 AU - Eugene P. Brandon AU - Weichun Lin AU - Kevin A. D'Amour AU - Donald P. Pizzo AU - Bertha Dominguez AU - Yoshie Sugiura AU - Silke Thode AU - Chien-Ping Ko AU - Leon J. Thal AU - Fred H. Gage AU - Kuo-Fen Lee Y1 - 2003/01/15 UR - http://www.jneurosci.org/content/23/2/539.abstract N2 - 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. ER -