title: Itm2a is a Pax3 target gene, expressed at sites of skeletal muscle formation in vivo.
abstract: 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.
authors: Département de Biologie du Développement, CNRS URA 2578, Institut Pasteur, Paris, France.
authors: Mounia
authors: M
authors: Lagha
authors: Alicia
authors: A
authors: Mayeuf-Louchart
authors: Ted
authors: T
authors: Chang
authors: Didier
authors: D
authors: Montarras
authors: Didier
authors: D
authors: Rocancourt
authors: Antoine
authors: A
authors: Zalc
authors: Jay
authors: J
authors: Kormish
authors: Kenneth S
authors: KS
authors: Zaret
authors: Margaret E
authors: ME
authors: Buckingham
authors: Frederic
authors: F
authors: Relaix
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism
chemical_list: C117398:Itm2a protein, mouse; D008565:Membrane Proteins; C497418:Myf5 protein, mouse; D051787:Myogenic Regulatory Factor 5; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; C068686:Pax3 protein, mouse
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