Disruption of the mouse Large gene in the enr and myd mutants results in nerve, muscle, and neuromuscular junction defects

Eleni N. Levedakou, Xiang Jun Chen, Betty Soliven, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The autosomal recessive neuromuscular disorder associated with the enervated (enr) mouse transgene insertion manifests impaired peripheral nerve regeneration due to defects in Schwann cells and resembles the myodystrophy (Largemyd) phenotype. Here we show that the enr transgene has integrated into Chr 8 approximately 160 kb downstream from the 3′ end of the Large gene disrupting its expression as confirmed by the lack of genetic complementation between Largemyd and enr mice, the very low Large mRNA levels in enr tissues and hypoglycosylation of α-dystroglycan, a known substrate of LARGE. Mutant nerve conduction and grip strength were impaired whereas sodium channel clustering at the nodes of Ranvier was unaffected. Interestingly, the mutant neuromuscular junctions displayed abnormal acetylcholine receptor clustering with reduced immunostaining for β-dystroglycan, laminin, agrin, MuSK, and to a lesser extent acetylcholinesterase and rapsyn. These data implicate LARGE in nerve, muscle, and neuromuscular junction function.

Original languageEnglish (US)
Pages (from-to)757-769
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume28
Issue number4
DOIs
StatePublished - Apr 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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