ErbB2 is required for muscle spindle and myoblast cell survival.
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.
Andrechek
Eran R
ER
Institute for Molecular Biology and Biotechnology, Department of Biology, McMaster University, Hamilton, Ontario, Canada.
Hardy
William R
WR
Girgis-Gabardo
Adele A
AA
Perry
Robert L S
RL
Butler
Richard
R
Graham
Frank L
FL
Kahn
Ronald C
RC
Rudnicki
Michael A
MA
Muller
William J
WJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D003402:Creatine Kinase / Q000235:genetics; D052283:Creatine Kinase, MM Form; D019426:Integrases / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009470:Muscle Spindles / Q000166:cytology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D011434:Proprioception / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics
D003402:Creatine Kinase; D052283:Creatine Kinase, MM Form; D019426:Integrases; D007527:Isoenzymes; D018719:Erb-b2 Receptor Tyrosine Kinases; D014764:Viral Proteins; C045073:Cre recombinase