{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:35:31Z","timestamp":1773916531467,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T00:00:00Z","timestamp":1268006400000},"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":[[2010,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>The <jats:italic>p53<\/jats:italic> pathway plays an important role in the regulation of apoptosis, osteoblast differentiation, skeletal development, and teratogenic sensitivity. The administration of cadmium chloride (CdCl<jats:sub>2<\/jats:sub>) on gestational day 9 in susceptible mouse strains causes postaxial forelimb ectrodactyly in a percentage of fetuses through unknown mechanisms. In this study, the hypothesis that the <jats:italic>p53<\/jats:italic> gene dosage might affect the incidence or severity of CdCl<jats:sub>2<\/jats:sub>\u2013induced forelimb ectrodactyly was examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Heterozygous <jats:italic>p53<\/jats:italic>\u2010null female mice, on the C57BL\/6J background known to be sensitive to CdCl<jats:sub>2<\/jats:sub>\u2010induced forelimb ectrodactyly, were mated with heterozygous males and then treated with a single intraperitoneal (ip) dose of CdCl<jats:sub>2<\/jats:sub> (4 mg \u00d7 kg<jats:sup>\u22121<\/jats:sup>) at embryonic day (ED) 9. Embryos and fetuses, genotyped using DNA isolated from the yolk sacs, were collected at ED10 and examined for the pattern of cell death in the limb buds or collected at ED18 and examined for limb malformations.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>In the wild type and heterozygous <jats:italic>p53<\/jats:italic> embryonic limb buds, CdCl<jats:sub>2<\/jats:sub>\u2010induced apoptosis involved mesenchymal cells as well as the apical ectodermal ridge (AER), whereas CdCl<jats:sub>2<\/jats:sub>\u2010induced apoptosis was restricted mainly to the AER in the homozygous <jats:italic>p53<\/jats:italic>\u2010null limb buds. No difference in the incidence or severity of forelimb ectrodactyly in the embryos of different <jats:italic>p53<\/jats:italic> genotypes was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION:<\/jats:title><jats:p>Despite the fact that CdCl<jats:sub>2<\/jats:sub> induced both p53\u2010dependent (in the mesenchyme) and p53\u2010independent (in the AER) cell death in the developing limb bud, CdCl<jats:sub>2<\/jats:sub>\u2010induced ectrodactyly was independent of the <jats:italic>p53<\/jats:italic> gene dosage at the studied time point. Birth Defects Research (Part A) 2010. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdra.20652","type":"journal-article","created":{"date-parts":[[2010,3,8]],"date-time":"2010-03-08T14:24:54Z","timestamp":1268058294000},"page":"223-227","source":"Crossref","is-referenced-by-count":5,"title":["Sensitivity to cadmium chloride\u2010induced forelimb ectrodactyly is independent of the <i>p53<\/i> gene\u2010dosage in the C57BL\/6J mouse"],"prefix":"10.1002","volume":"88","author":[{"given":"Ahmed F.","family":"Elsaid","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled M. 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