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In this study, we generated a novel <jats:italic>Scx<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic><\/jats:sup> knock-in (KI) allele, by in-frame replacement of most of <jats:italic>Scx<\/jats:italic> exon 1 with <jats:italic>Cre recombinase (Cre<\/jats:italic>), to drive <jats:italic>Cre<\/jats:italic> expression using <jats:italic>Scx<\/jats:italic> promoter and to inactivate the endogenous <jats:italic>Scx<\/jats:italic>. Reflecting the intensity and duration of endogenous expression, Cre-mediated excision occurs in tendinous and ligamentous tissues persistently expressing <jats:italic>Scx<\/jats:italic>. Expression of tenomodulin, a marker of mature tenocytes and ligamentocytes, was almost absent in tendons and ligaments of <jats:italic>Scx<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic>\/<jats:italic>Cre<\/jats:italic><\/jats:sup> KI mice lacking <jats:italic>Scx<\/jats:italic> to indicate defective maturation. In homozygotes, the transiently <jats:italic>Scx<\/jats:italic>-expressing entheseal regions such as the rib cage, patella cartilage, and calcaneus were small and defective and cartilaginous tuberosity was missing. Decreased Sox9 expression and phosphorylation of Smad1\/5 and Smad3 were also observed in the developing entheseal cartilage, patella, and deltoid tuberosity of <jats:italic>Scx<\/jats:italic><jats:sup><jats:italic>Cre<\/jats:italic>\/<jats:italic>Cre<\/jats:italic><\/jats:sup> KI mice. These results highlighted the functional importance of both transient and persistent expression domains of <jats:italic>Scx<\/jats:italic> for proper integration of the musculoskeletal components.<\/jats:p>","DOI":"10.1038\/srep45010","type":"journal-article","created":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T12:03:20Z","timestamp":1490184200000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":104,"title":["Scleraxis is required for maturation of tissue domains for proper integration of the musculoskeletal system"],"prefix":"10.1038","volume":"7","author":[{"given":"Yuki","family":"Yoshimoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aki","family":"Takimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuji","family":"Hiraki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Kondoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chisa","family":"Shukunami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,22]]},"reference":[{"key":"BFsrep45010_CR1","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.1242\/dev.121.4.1099","volume":"121","author":"P Cserjesi","year":"1995","unstructured":"Cserjesi, P. et al. 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