Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers

Misook Oh, Igor I. Rybkin, Victoria Copeland, Michael P. Czubryt, John M. Shelton, Eva Van Rooij, James A Richardson, Joseph A Hill, Leon J. De Windt, Rhonda S Bassel-Duby, Eric N Olson, Beverly A Rothermel

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Skeletal muscles are a mosaic of slow and fast twitch myofibers. During embryogenesis, patterns of fiber type composition are initiated that change postnatally to meet physiological demand. To examine the role of the protein phosphatase calcineurin in the initiation and maintenance of muscle fiber types, we used a "Flox-ON" approach to obtain muscle-specific overexpression of the modulatory calcineurin-interacting protein 1 (MCIP1/DSCR1), an inhibitor of calcineurin. Myo-Cre transgenic mice with early skeletal muscle-specific expression of Cre recombinase were used to activate the Flox-MCIP1 transgene. Contractile components unique to type 1 slow fibers were absent from skeletal muscle of adult Myo-Cre/Flox-MCIP1 mice, whereas oxidative capacity, myoglobin content, and mitochondrial abundance were unaltered. The soleus muscles of Myo-Cre/Flox-MCIP1 mice fatigued more rapidly than the wild type as a consequence of the replacement of the slow myosin heavy chain MyHC-1 with a fast isoform, MyHC-2A. MyHC-1 expression in Myo-Cre/Flox-MCIP1 embryos and early neonates was normal. These results demonstrate that developmental patterning of slow fibers is independent of calcineurin, while the maintenance of the slow-fiber phenotype in the adult requires calcineurin activity.

Original languageEnglish (US)
Pages (from-to)6629-6638
Number of pages10
JournalMolecular and cellular biology
Issue number15
StatePublished - Aug 2005

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Calcineurin is necessary for the maintenance but not embryonic development of slow muscle fibers'. Together they form a unique fingerprint.

Cite this