Muscle regeneration and myogenic differentiation defects in mice lacking TIS7.
The tetradecanoyl phorbol acetate-induced sequence 7 gene (tis7) is regulated during cell fate processes and functions as a transcriptional coregulator. Here, we describe the generation and analysis of mice lacking the tis7 gene. Surprisingly, TIS7 knockout mice show no gross histological abnormalities and are fertile. Disruption of the tis7 gene by homologous recombination delayed muscle regeneration and altered the isometric contractile properties of skeletal muscles after muscle crush damage in TIS7(-/-) mice. Cultured primary myogenic satellite cells (MSCs) from TIS7(-/-) mice displayed marked reductions in differentiation potential and fusion index in a strictly cell-autonomous fashion. Loss of TIS7 caused the down-regulation of muscle-specific genes, such as those for MyoD, myogenin, and laminin-alpha2. Fusion potential in TIS7(-/-) MSCs could be rescued by TIS7 expression or laminin supplementation. Therefore, TIS7 is not essential for mouse development but plays a novel regulatory role during adult muscle regeneration.
Vadivelu
Santhosh K
SK
Institute for Anatomy, Histology, and Embryology, Department of Histology and Molecular Cell Biology, Medical University Innsbruck, A-6020 Innsbruck, Austria.
Kurzbauer
Robert
R
Dieplinger
Benjamin
B
Zweyer
Margit
M
Schafer
Ralf
R
Wernig
Anton
A
Vietor
Ilja
I
Huber
Lukas A
LA
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D005456:Fluorescent Dyes / Q000378:metabolism; D018390:Gene Targeting; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D012038:Regeneration / Q000502:physiology*
D005456:Fluorescent Dyes; C490044:Ifrd1 protein, mouse; D017874:Immediate-Early Proteins; D008565:Membrane Proteins