Shp2 is dispensable in the formation and maintenance of the neuromuscular junction

Xian Ping Dong, Xiao Ming Li, Tian Ming Gao, Eric E. Zhang, Gen Sheng Feng, Wen C. Xiong, Lin Mei

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

SHP2, a protein tyrosine phosphatase with two SH2 domains, has been implicated in regulating acetylcholine receptor (AChR) gene expression and cluster formation in cultured muscle cells. To understand the role of SHP2 in neuromuscular junction (NMJ) formation in vivo, we generated muscle-specific deficient mice by using a loxP/Cre strategy since Shp2 null mutation causes embryonic lethality. Shp2floxed/floxed mice were crossed with mice expressing the Cre gene under the control of the human skeletal α-actin (HSA) promoter. Expression of SHP2 was reduced or diminished specifically in skeletal muscles of the conditional knockout (CKO) mice. The mutant mice were viable and fertile, without apparent muscle defects. The mRNA of the AChR α subunit and AChR clusters in CKO mice were localized in a narrow central region surrounding the phrenic nerve primary branches, without apparent change in intensity. AChR clusters colocalized with markers of synaptic vesicles and Schwann cells, suggesting proper differentiation of presynaptic terminals and Schwann cells. In comparison with age-matched littermates, no apparent difference was observed in the size and length of AChR clusters in CKO mice. Both the frequency and amplitude of mEPPs in CKO mice were similar to those in controls, suggesting normal neurotransmission when SHP2 was deficient. These results suggest that Shp2 is not required for NMJ formation and/or maintenance.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalNeuroSignals
Volume15
Issue number2
DOIs
StatePublished - Aug 1 2006

Keywords

  • Agrin
  • Conditional knockout
  • Formation
  • MuSK
  • Neuromuscular junction
  • SHP2
  • Synapse
  • Transcription

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience

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    Dong, X. P., Li, X. M., Gao, T. M., Zhang, E. E., Feng, G. S., Xiong, W. C., & Mei, L. (2006). Shp2 is dispensable in the formation and maintenance of the neuromuscular junction. NeuroSignals, 15(2), 53-63. https://doi.org/10.1159/000094484