{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,15]],"date-time":"2024-09-15T13:00:58Z","timestamp":1726405258722},"reference-count":35,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T00:00:00Z","timestamp":1228953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>BACKGROUND:<\/jats:bold><jats:italic>Dominant hemimelia (Dh)<\/jats:italic>is an autosomal dominant mutation that arose spontaneously in mice.<jats:italic>Dh<\/jats:italic>animals are asplenic and they exhibit asymmetric hindlimb defects in association with reduced numbers of lumbar vertebrae. These defects suggest that<jats:italic>Dh<\/jats:italic>acts early in embryonic development to affect patterning of the anterior\u2010posterior (A\u2010P) and left\u2010right axes. This study was undertaken to determine whether retinoic acid (RA), which is involved in A\u2010P patterning and coordination of bilaterally synchronized somitogenesis, affects phenotypic expression of the<jats:italic>Dh<\/jats:italic>gene.<jats:bold>METHODS:<\/jats:bold>Thirty\u2010four pregnant females were given, by oral intubation, a single dose of 50 or 75 mg all\u2010trans RA per kilogram body weight at GD 9, 10, or 11. The pregnant females were then euthanized at GD 18 and fetuses removed by cesarean section. A total of 326 fetuses were identified by phenotype and linked DNA and their skeletons were analyzed.<jats:bold>RESULTS:<\/jats:bold>There was a differential effect of RA on the axial skeleton and hindlimb of<jats:italic>Dh<\/jats:italic>\/+ mice as compared to their wild\u2010type littermates. Dose\u2010 and stage\u2010specific effects on sternebrae and vertebrae were observed.<jats:bold>CONCLUSIONS:<\/jats:bold>The effects of RA dosing on numbers of sternebrae and vertebrae suggest that<jats:italic>Dh<\/jats:italic>embryos have a primary defect in retinoid\u2010mediated A\u2010P patterning. Dosing with RA may produce the observed effects on phenotypic expression of<jats:italic>Dh<\/jats:italic>\/+ by indirectly or directly modifying an already existing altered<jats:italic>Hox<\/jats:italic>expression pattern. As the relationship between axial patterning and the asymmetric limb is unknown,<jats:italic>Dh<\/jats:italic>is an important model for studying this relationship. Birth Defects Research (Part A), 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/bdra.20528","type":"journal-article","created":{"date-parts":[[2008,12,11]],"date-time":"2008-12-11T17:56:05Z","timestamp":1229018165000},"page":"36-41","source":"Crossref","is-referenced-by-count":2,"title":["Effects of retinoic acid on<i>Dominant hemimelia<\/i>expression in mice"],"prefix":"10.1002","volume":"85","author":[{"given":"Mary H.","family":"Owen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise M.","family":"Ryan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lewis B.","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,12,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.855001"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002040302"},{"key":"e_1_2_6_4_1","first-page":"16","article-title":"Dominant hemimelia","volume":"11","author":"Carter TC","year":"1954","journal-title":"Dh. 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