ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival

Abstract

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.

We thank Dinsdale Gooden for oligonucleotide synthesis and Brian Allore for automated DNA sequence analysis (MOBIX Central Facility, McMaster University). We thank John Hassell for critically reviewing the manuscript and Monica Graham for technical support.

Funding for this work was provided by the MRC grant MT10594. M.A.R. is supported by grants from the NIH, CIHR, and Muscular Dystrophy Association.