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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-α2. 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.
We thank all of the employees of the animal house facility of the Institute of Molecular Pathology and especially E. Wagner and H. C. Theussl for help and advice in generating and maintaining the knockout mice. We thank M. Busslinger, R. Vanishree, and B. Flucher for critically reading and discussing the manuscript. We also thank M. Cotten for the indispensable work in generating recombinant Celo-TIS7 virus. We are grateful to C. Seiser, T. Partridge, and R. Bittner for many helpful discussions and suggestions during the early phases of this project. We thank K. Pfaller, K. Paiha, S. Briel, J. Heckroth, and R. Kofler for excellent technical assistance.
This work was supported by Boehringer Ingelheim, Austrian Science Foundation grant FWF,P13577-GEN, and the Austrian Genome Program (GEM-AU).