Original Paper

Shp2 Is Dispensable in the Formation and Maintenance of the Neuromuscular Junction
Xian-Ping Dong^a, Xiao-Ming Li^a, Tian-Ming Gao^a, Eric E. Zhang^b, Gen-Sheng Feng^b, Wen C. Xiong^a, Lin Mei<sup>a

a</sup>Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Ga.,
^bProgram in Signal Transduction, The Burnham Institute for Medical Research, La Jolla, Calif., USA

Address of Corresponding Author

Neurosignals 2006/2007;15:53-63 (DOI: 10.1159/000094484)

  Key Words

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

  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 mus cle-specific deficient mice by using a loxP/Cre strategy since Shp2 null mutation causes embryonic lethality. Shp2^{floxed/floxed} mice were crossed with mice expressing the Cre gene under the control of the human skeletal -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 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.

Copyright © 2006 S. Karger AG, Basel

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  Author Contacts

Lin Mei
Program of Developmental Neurobiology
Institute of Molecular Medicine and Genetics, Medical College of Georgia
CB2803, 1120 15th Street, Augusta, GA 30912 (USA)
Tel. +1 706 721 8775, Fax +1 706 721 8685, E-Mail lmei@mcg.edu

  Article Information

Received: March 31, 2006
Accepted: May 4, 2006
Published online: July 11, 2006
Number of Print Pages : 11
Number of Figures : 6, Number of Tables : 0, Number of References : 69

  Publication Details

Neurosignals

Vol. 15, No. 2, Year 2006/2007 (Cover Date: August 2006)

Journal Editor: Ip, N.Y. (Hong Kong)
ISSN: 1424-862X (print), 1424-8638 (Online)

For additional information: http://www.karger.com/NSG

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