期刊
PLOS ONE
卷 8, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0063143
关键词
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资金
- INSERM Avenir Program
- Association Francaise Contre les Myopathies (AFM)
- Association Institut de Myologie
- Ligue Nationale Contre le Cancer (LNCC)
- Association pour la Recherche Contre le Cancer (ARC)
- Fondation pour la Recherche Medicale, Institut National du Cancer (INCa)
- European Union [241440]
- Pasteur Institute
- CNRS [URA 2578, 200720]
- AFM
- Optistem [223098]
- Human Frontier Science Program (HFSP)
The paired-box homeodomain transcription factor Pax3 is a key regulator of the nervous system, neural crest and skeletal muscle development. Despite the important role of this transcription factor, very few direct target genes have been characterized. We show that Itm2a, which encodes a type 2 transmembrane protein, is a direct Pax3 target in vivo, by combining genetic approaches and in vivo chromatin immunoprecipitation assays. We have generated a conditional mutant allele for Itm2a, which is an imprinted gene, by flanking exons 2-4 with loxP sites and inserting an IRESnLacZ reporter in the 3' UTR of the gene. The LacZ reporter reproduces the expression profile of Itm2a, and allowed us to further characterize its expression at sites of myogenesis, in the dermomyotome and myotome of somites, and in limb buds, in the mouse embryo. We further show that Itm2a is not only expressed in adult muscle fibres but also in the satellite cells responsible for regeneration. Itm2a mutant mice are viable and fertile with no overt phenotype during skeletal muscle formation or regeneration. Potential compensatory mechanisms are discussed.
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