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Molecular and Cellular Biology, July 2002, p. 4714-4722, Vol. 22, No. 13
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.13.4714-4722.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival

Eran R. Andrechek,1 William R. Hardy,2 Adele A. Girgis-Gabardo,1 Robert L. S. Perry,1 Richard Butler,3 Frank L. Graham,1 Ronald C. Kahn,4 Michael A. Rudnicki,5 and William J. Muller1,3*

Institute for Molecular Biology and Biotechnology, Department of Biology,1 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario,3 Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto,2 Ottawa Health Research Institute, Ottawa, Canada,5 Joslin Diabetes Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts4

Received 27 November 2001/ Returned for modification 21 January 2002/ Accepted 26 March 2002

Signaling mediated by ErbB2 is thought to play a critical role in numerous developmental processes. However, due to the embryonic lethality associated with the germ line inactivation of erbB2, its role in adult tissues remains largely obscure. Given the expression of ErbB2 at the neuromuscular junction, we have created a muscle-specific knockout to assess its role there. This resulted in viable mice with a progressive defect in proprioception due to loss of muscle spindles. Interestingly, a partial reduction of ErbB2 levels also reduced the number of muscle spindles. Although histological analysis of the muscle revealed an otherwise normal architecture, induction of muscle injury revealed a defect in muscle regeneration. Consistent with these observations, primary myoblasts lacking ErbB2 exhibit extensive apoptosis upon differentiation into myofibers. Taken together, these results illustrate a dual role for ErbB2 in both muscle spindle maintenance and survival of myoblasts.

* Corresponding author. Mailing address: Institute for Molecular Biology and Biotechnology, Department of Biology, McMaster University, Hamilton, Ontario, Canada L8S 4K1. Phone: (905) 525-9140, ext. 27261. Fax: (905) 521-2955. E-mail: mullerw{at}mcmail.cis.mcmaster.ca.

Molecular and Cellular Biology, July 2002, p. 4714-4722, Vol. 22, No. 13
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.13.4714-4722.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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