Myogenin induces higher oxidative capacity in pre-existing mouse muscle fibres after somatic DNA transfer.
Muscle is a permanent tissue, and in the adult pronounced changes can occur in pre-existing fibres without the formation of new fibres. Thus, the mechanisms responsible for phenotype transformation in the adult might be distinct from mechanisms regulating muscle differentiation during muscle formation and growth. Myogenin is a muscle-specific, basic helix-loop-helix transcription factor that is important during early muscle differentiation. It is also expressed in the adult, where its role is unknown. In this study we have overexpressed myogenin in glycolytic fibres of normal adult mice by electroporation and single-cell intracellular injection of expression vectors. Myogenin had no effects on myosin heavy chain fibre type, but induced a considerable increase in succinate dehydrogenase and NADH dehydrogenase activity, with some type IIb fibres reaching the levels observed histochemically in normal type IIx and IIa fibres. mRNA levels for malate dehydrogenase were similarly altered. The size of the fibres overexpressing myogenin was reduced by 30-50 %. Thus, the transfected fibres acquired a phenotype reminiscent of the phenotype obtained by endurance training in man and other animals, with a higher oxidative capacity and smaller size. We conclude that myogenin can alter pre-existing glycolytic fibres in the intact adult animal.
Ekmark
Merete
M
Department of Biology, University of Oslo, PO Box 1051, Blindern, N-0316 Oslo, Norway.
Grønevik
Eirik
E
Schjerling
Peter
P
Gundersen
Kristian
K
D000818:Animals; D015152:Blotting, Northern; D046508:Culture Techniques; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D018274:Electroporation; D005260:Female; D018014:Gene Transfer Techniques; D006651:Histocytochemistry; D007763:Lac Operon / Q000235:genetics; D051379:Mice; D008845:Microinjections; D018485:Muscle Fibers, Skeletal / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018008:Myogenin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014162:Transfection; D001616:beta-Galactosidase / Q000378:metabolism
C503801:Myog protein, mouse; D018008:Myogenin; D012333:RNA, Messenger; D004247:DNA; D013385:Succinate Dehydrogenase; D001616:beta-Galactosidase