Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization

A1 Journal article (refereed)


Internal Authors/Editors


Publication Details

List of Authors: Stone MR, O'Neill A, Lovering RM, Strong J, Resneck WG, Reed PW, Toivola DM, Ursitti JA, Omary MB, Bloch RJ
Publisher: COMPANY OF BIOLOGISTS LTD
Publication year: 2007
Journal: Journal of Cell Science
Journal acronym: J CELL SCI
Volume number: 120
Start page: 3999
End page: 4008
Number of pages: 10
ISSN: 0021-9533


Abstract

Intermediate filaments, composed of desmin and of keratins, play important roles in linking contractile elements to each other and to the sarcolemma in striated muscle. We examined the contractile properties and morphology of fast-twitch skeletal muscle from mice lacking keratin 19. Tibialis anterior muscles of keratin-19-null mice showed a small but significant decrease in mean fiber diameter and in the specific force of tetanic contraction, as well as increased plasma creatine kinase levels. Costameres at the sarcolemma of keratin-19-null muscle, visualized with antibodies against spectrin or dystrophin, were disrupted and the sarcolemma was separated from adjacent myofibrils by a large gap in which mitochondria accumulated. The costameric dystrophin-dystroglycan complex, which co-purified with gamma-actin, keratin 8 and keratin 19 from striated muscles of wild-type mice, co-purified with gamma-actin but not keratin 8 in the mutant. Our results suggest that keratin 19 in fast-twitch skeletal muscle helps organize costameres and links them to the contractile apparatus, and that the absence of keratin 19 disrupts these structures, resulting in loss of contractile force, altered distribution of mitochondria and mild myopathy. This is the first demonstration of a mammalian phenotype associated with a genetic perturbation of keratin 19.


Keywords

costamere, Desmin, dystrophin, sarcolemma, Sarcomere, spectrin

Last updated on 2019-15-10 at 02:34

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