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CFC belongs to a group of syndromes known as RASopathies. Skeletal muscle hypotonia is a ubiquitous phenotype of RASopathies, especially in CFC syndrome. To better understand the underlying mechanisms for the skeletal myopathy in CFC, a mouse model with an activating <jats:italic>Braf<\/jats:italic><jats:sup><jats:italic>L597V<\/jats:italic><\/jats:sup> allele was utilized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The activating <jats:italic>Braf<\/jats:italic><jats:sup><jats:italic>L597V<\/jats:italic><\/jats:sup> allele resulted in phenotypic alterations in skeletal muscle characterized by a reduction in fiber size which leads to a reduction in muscle size which are functionally weaker. MAPK pathway activation caused inhibition of myofiber differentiation during embryonic myogenesis and global transcriptional dysregulation of developmental pathways. Inhibition in differentiation can be rescued by MEK inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A skeletal myopathy was identified in the CFC <jats:italic>Braf<\/jats:italic><jats:sup><jats:italic>L597V<\/jats:italic><\/jats:sup> mouse validating the use of models to study the effect of Ras\/MAPK dysregulation on skeletal myogenesis. RASopathies present a novel opportunity to identify new paradigms of myogenesis and further our understanding of Ras in development. Rescue of the phenotype by inhibitors may help advance the development of therapeutic options for RASopathy patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.309","type":"journal-article","created":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T08:07:13Z","timestamp":1612166833000},"page":"1074-1095","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Ras\/<scp>MAPK<\/scp> dysregulation in development causes a skeletal myopathy in an activating <scp><i>Braf<\/i><sup><i>L597V<\/i><\/sup><\/scp> mouse model for cardio\u2010facio\u2010cutaneous syndrome"],"prefix":"10.1002","volume":"250","author":[{"given":"Yoshiko","family":"Maeda","sequence":"first","affiliation":[{"name":"Department of Pediatrics University of California Davis  Sacramento California USA"},{"name":"UC Davis MIND Institute  Sacramento California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William 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