{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T01:38:13Z","timestamp":1791077893987,"version":"4.1.0"},"reference-count":0,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2001,12,25]],"date-time":"2001-12-25T00:00:00Z","timestamp":1009238400000},"content-version":"vor","delay-in-days":572,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>NK homeobox genes have been shown to play important roles in cell\u2010type specification and organogenesis. Murine <jats:italic>Bapx1<\/jats:italic>, a member of NK homeobox gene family, is expressed in all the cartilageous tissues that undergo endochondral bone formation, and in gut mesentery during embryogenesis, suggesting that <jats:italic>Bapx1<\/jats:italic> may be a key transcription factor ragulating the development of these organs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We generated <jats:italic>Bapx1<\/jats:italic>\u2010deficient mice by gene targeting. <jats:italic>Bapx1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice exhibited lethal skeletal dysplasia, with abnormal development of the vertebral column and some craniofacial bones, accompanied with asplenia and gastroduodenal malformation. We showed that the proliferative activity of the sclerotome cells, forming the vertebral column, was significantly reduced in <jats:italic>Bapx1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> embryos. The sclerotome cells of the mutants appeared to migrate and condense normally, but subsequent differentiation into the mature vertebral bodies and intervertebral discs were affected. The sclerotome cells in the vertebral bodies failed to differentiate into hypertrophic chondrocytes, as revealed by the undetected expression of <jats:italic>Col10a1<\/jats:italic> and <jats:italic>Osteopontin<\/jats:italic>, and the sclerotome cells in the intervertebral discs failed to express the typical extracellular matrix proteins <jats:italic>Col2a1<\/jats:italic>, <jats:italic>Col9a2<\/jats:italic> and <jats:italic>aggrecan<\/jats:italic>. Furthermore, we investigated the effect of loss of <jats:italic>Bapx1<\/jats:italic> on the expression of some transcription factors, identified to be expressed in the developing sclerotome and be required for normal development of the vertebral column. Among them, we found that the expression of <jats:italic>MFH\u20101<\/jats:italic> (<jats:italic>mesenchyme forkhead\u20101<\/jats:italic>), which was reported to regulate the proliferation and differentiation of sclerotome cells, was significantly reduced in ventromedial sclerotome cells in <jats:italic>Bapx1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our analysis provided evidence that <jats:italic>Bapx1<\/jats:italic> was indispensable for normal development of ventromedial structure of vertebral column and some of craniofacial bones, splenogenesis and morphogenesis of gastroduodenal tract.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2443.2000.00339.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T22:46:08Z","timestamp":1047422768000},"page":"499-513","source":"Crossref","is-referenced-by-count":100,"title":["Targeted disruption of the homeobox transcription factor <i>Bapx1<\/i> results in lethal skeletal dysplasia with asplenia and gastroduodenal malformation"],"prefix":"10.1111","volume":"5","author":[{"given":"Hiroshi","family":"Akazawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Issei","family":"Komuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshinobu","family":"Sugitani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Yazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuo","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2001,12,25]]},"container-title":["Genes to Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2443.2000.00339.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2443.2000.00339.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2443.2000.00339.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,7]],"date-time":"2023-10-07T04:31:59Z","timestamp":1696653119000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2443.2000.00339.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2000,6]]}},"alternative-id":["10.1046\/j.1365-2443.2000.00339.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2443.2000.00339.x","archive":["Portico"],"relation":{},"ISSN":["1356-9597","1365-2443"],"issn-type":[{"value":"1356-9597","type":"print"},{"value":"1365-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,6]]}}}