Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2

Osamu Nakagawa, Michael Arnold, Masayo Nakagawa, Hideaki Hamada, John M. Shelton, Hajime Kusano, Thomas M. Harris, Geoffrey Childs, Kevin P. Campbell, James A. Richardson, Ichizo Nishino, Eric N. Olson

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. However, signaling pathways acting downstream of MEF2 are largely unknown. Here, we performed a microarray analysis using Mef2c-null mouse embryos and identified a novel MEF2-regulated gene encoding a muscle-specific protein kinase, Srpk3, belonging to the serine arginine protein kinase (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins. The Srpk3 gene is specifically expressed in the heart and skeletal muscle from embryogenesis to adulthood and is controlled by a muscle-specific enhancer directly regulated by MEF2. Srpk3-null mice display a new entity of type 2 fiber-specific myopathy with a marked increase in centrally placed nuclei; while transgenic mice overexpressing Srpk3 in skeletal muscle show severe myofiber degeneration and early lethality. We conclude that normal muscle growth and homeostasis require MEF2-dependent signaling by Srpk3.

Original languageEnglish (US)
Pages (from-to)2066-2077
Number of pages12
JournalGenes and Development
Issue number17
StatePublished - Sep 1 2005
Externally publishedYes


  • Centronuclear myopathy
  • Myocyte enhancer factor 2
  • Serine arginine protein kinase (SRPK)
  • Stk23/Srpk3
  • Transcriptional regulation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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