title: A cytoskeletal tropomyosin can compromise the structural integrity of skeletal muscle.
abstract: We have identified a number of extra-sarcomeric actin filaments defined by cytoskeletal tropomyosin (Tm) isoforms. Expression of a cytoskeletal Tm (Tm3) not normally present in skeletal muscle in a transgenic mouse resulted in muscular dystrophy. In the present report we show that muscle pathology in this mouse is late onset (between 2 and 6 months of age) and is predominately in the back and paraspinal muscles. In the Tm3 mice, Evans blue dye uptake in muscle and serum levels of creatine kinase were markedly increased following downhill exercise, and the force drop following a series of lengthening contractions in isolated muscles (extensor digitorum longus) was also significantly increased in these mice. These results demonstrate that expression of an inappropriate Tm in skeletal muscle results in increased susceptibility to contraction-induced damage. The extra-sarcomeric actin cytoskeleton therefore may have an important role in protecting the muscle from contractile stress.
authors.affiliation: Department of Anatomy, School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Kee
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D003599:Cytoskeleton / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms / Q000378:metabolism; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; C411923:Tpm3 protein, mouse; D014335:Tropomyosin; D003402:Creatine Kinase