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

MR Stone, A O'Neill, RM Lovering, J Strong, WG Resneck, PW Reed, Diana Toivola, JA Ursitti, MB Omary, RJ Bloch

Research output: Contribution to journalArticleScientificpeer-review

64 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)3999–4008
Number of pages10
JournalJournal of Cell Science
Volume120
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

Keywords

  • costamere
  • dystrophin
  • sarcolemma
  • spectrin
  • Desmin
  • Sarcomere

Cite this