Srpk3-null mice display type 2 fiber-specific myopathy with centrally placed nuclei, while Srpk3 overexpression causes severe myofiber degeneration and early lethality.
Does Srpk3 deletion or overexpression affect muscle growth and homeostasis in mice?
Identifies Srpk3 as a critical MEF2-dependent signaling molecule required for normal muscle growth and homeostasis.
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.
Nakagawa et al. (Thu,) conducted a other in Centronuclear myopathy. Srpk3 gene deletion or overexpression vs. Wild-type mice was evaluated on Muscle phenotype and viability. Srpk3-null mice display type 2 fiber-specific myopathy with centrally placed nuclei, while Srpk3 overexpression causes severe myofiber degeneration and early lethality.