Abstract
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.
MeSH Terms
Animals
Cell Differentiation/physiology
Cells, Cultured
Coculture Techniques
Fluorescent Dyes/metabolism
Gene Targeting
Immediate-Early Proteins/genetics,metabolism
Membrane Proteins/genetics,metabolism
Mice
Mice, Knockout
Muscle Contraction/physiology
Muscle, Skeletal/cytology,physiology
Myoblasts/cytology,physiology
Phenotype
Regeneration/physiology
Chemicals
Fluorescent Dyes
Ifrd1 protein, mouse
Immediate-Early Proteins
Membrane Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Vadivelu Santhosh K
Institute for Anatomy, Histology, and Embryology, Department of Histology and Molecular Cell Biology, Medical University Innsbruck, A-6020 Innsbruck, Austria.
Kurzbauer Robert
Dieplinger Benjamin
Zweyer Margit
Schafer Ralf
Wernig Anton
Vietor Ilja
Huber Lukas A
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