Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors

Virginia Barone, Federica Bertocchini, Roberto Bottinelli, Feliciano Protasi, Paul D. Allen, Clara Franzini Armstrong, Carlo Reggiani, Vincenzo Sorrentino

Research output: Contribution to journalArticle

Abstract

Skeletal muscle contraction is triggered by the release of Ca2+ from the sarcoplasmic reticulum through the type 1 ryanodine receptor (RyR1). Recently it has been shown that also the type 3 isoform of ryanodine receptor (RyR3), which is expressed in some mammalian skeletal muscles, may participate in the regulation of skeletal muscle contraction. Here we report the generation and the characterization of double mutant mice carrying a targeted disruption of both the RyR1 and the RyR3 genes (RyR1(-/-);RyR3(-/-)). Skeletal muscles from mice homozygous for both mutations are unable to contract in response to caffeine and to ryanodine. In addition, they show a very poor capability to develop tension when directly activated with micromolar [Ca2+](i) after membrane permeabilization which indicates either poor development or degeneration of the myofibrils. This was confirmed by biochemical analysis of contractile proteins. Electron microscopy confirms small size of myofibrils and shows complete absence of feet (RyRs) in the junctional SR.

Original languageEnglish
Pages (from-to)160-164
Number of pages5
JournalFEBS Letters
Volume422
Issue number2
DOIs
Publication statusPublished - Jan 30 1998

Keywords

  • Knockout mouse
  • Prenatal muscular development
  • Ryanodine receptor type 1 and type 3
  • Skeletal muscle contraction

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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  • Cite this

    Barone, V., Bertocchini, F., Bottinelli, R., Protasi, F., Allen, P. D., Franzini Armstrong, C., Reggiani, C., & Sorrentino, V. (1998). Contractile impairment and structural alterations of skeletal muscles from knockout mice lacking type 1 and type 3 ryanodine receptors. FEBS Letters, 422(2), 160-164. https://doi.org/10.1016/S0014-5793(98)00003-9