Aberrant patterning of neuromuscular synapses in choline acetyltransferase-deficient mice

Eugene P. Brandon, Weichun Lin, Kevin A. D'Amour, Donald P. Pizzo, Bertha Dominguez, Yoshie Sugiura, Silke Thode, Chien Ping Ko, Leon J. Thal, Fred H. Gage, Kuo Fen Lee

Research output: Contribution to journalArticlepeer-review

144 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)539-549
Number of pages11
JournalJournal of Neuroscience
Issue number2
StatePublished - Jan 15 2003


  • Acetylcholine
  • Choline acetyltransferase
  • Gene knock-out
  • Mice
  • Neural development
  • Neuromuscular

ASJC Scopus subject areas

  • Neuroscience(all)


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