{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:45:52Z","timestamp":1782114352372,"version":"3.54.5"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T00:00:00Z","timestamp":1549238400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The mutant chondrodysplasia (<jats:italic>cho<\/jats:italic>) is a cartilage\u2010targeting disorder in C57BL mice that results in dwarfing and other malformations stemming from this collagenopathy. Clarke Fraser made the discovery of the mutation accidentally in the early 1960s during the thalidomide tragedy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>For this review we identified key research on <jats:italic>cho<\/jats:italic> as since its discovery. Relevant data were compiled to make a comprehensive review that details discoveries associated with the <jats:italic>cho<\/jats:italic> mutation, that describes the associated phenotypes and molecular mechanisms, and that provides a discussion surrounding its current clinical relevance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mechanistically, <jats:italic>cho<\/jats:italic> acts by hindering chondrogenesis and endochondral bone formation. The phenotype results from a 1\u2010nt deletion in the gene encoding the alpha 1 chain of type XI collagen. For more than half a century, researchers have studied the pathogenesis of the <jats:italic>cho<\/jats:italic> mutation in relation to a variety of mouse models of human birth defects and disease. These studies have resulted in several discoveries linking <jats:italic>cho<\/jats:italic> with such human disorders as dwarfism, tracheal stenosis, cleft palate, pulmonary hypoplasia, and osteoarthritis (OA).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The study of <jats:italic>cho<\/jats:italic> has led to numerous advances in understanding human birth defects, congenital disorders, and adult human disease. The most recent studies have suggested a role for the TGF\u2010Beta, HtrA1, Ddr2, and Mmp\u201013 pathway in the degradation of articular cartilage and the development of OA in <jats:italic>cho\/+<\/jats:italic> mice. We have shown that the anti\u2010hypertension drug Losartan is a TGF\u2010Beta blocker that could be used to treat OA in Stickler syndrome, and thereby rescue the WT phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.1473","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T10:44:25Z","timestamp":1549363465000},"page":"237-247","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Understanding chondrodysplasia (<i>cho<\/i>): A comprehensive review of <i>cho<\/i> as an animal model of birth defects, disorders, and molecular mechanisms"],"prefix":"10.1002","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6193-7505","authenticated-orcid":false,"given":"Robert E.","family":"Seegmiller","sequence":"first","affiliation":[{"name":"Department of Physiology and Developmental Biology Brigham Young University  Provo Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron","family":"Foster","sequence":"additional","affiliation":[{"name":"Department of Physiology and Developmental Biology Brigham Young University  Provo Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared L.","family":"Burnham","sequence":"additional","affiliation":[{"name":"Department of Physiology and Developmental Biology Brigham Young University  Provo Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,2,4]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200003000-00025"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/302585"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.54.8.614"},{"issue":"1","key":"e_1_2_11_5_1","first-page":"165","article-title":"Disproportionate micromelia (Dmm): An incomplete dominant mouse dwarfism with abnormal cartilage matrix","volume":"62","author":"Brown K. 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