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We aimed to investigate the function of CYP17A1 and its impact on atherosclerosis in mice. At 4\u20136 months, CYP17A1-deficient mice were viable, with a KO:Het:WT ratio approximating the expected Mendelian ratio of 1:2:1. All <jats:italic>Cyp17a1<\/jats:italic> knockout (KO) mice were phenotypically female; however, 58% were Y chromosome-positive, resembling the phenotype of human CYP17A1 deficiency, leading to 46,XY differences\/disorders of sex development (DSD). Both male and female homozygous KO mice were infertile, due to\u00a0abnormal genital organs. Plasma steroid analyses revealed a complete lack of testosterone in XY-KO mice and marked accumulation of progesterone in XX-KO mice. Elevated corticosterone levels were observed in both XY and XX KO mice. In addition, <jats:italic>Cyp17a1<\/jats:italic> heterozygous mice were also backcrossed onto an <jats:italic>Apoe<\/jats:italic> KO atherogenic background and fed a western-type diet (WTD) to study the effects of CYP17A1 on atherosclerosis. <jats:italic>Cyp17a1<\/jats:italic> x <jats:italic>Apoe<\/jats:italic> double KO XY mice developed more atherosclerotic lesions than <jats:italic>Apoe<\/jats:italic> KO male controls, regardless of diet (standard or WTD). Increased atherosclerosis in CYP17A1 XY KO mice lacking testosterone was associated with altered lipid profiles. In mice, CYP17A1 deficiency interferes with sex differentiation. Our data also demonstrate its key role in lipidomic profile, and as a risk factor in the pathogenesis of atherosclerosis.<\/jats:p>","DOI":"10.1038\/s41598-020-65601-0","type":"journal-article","created":{"date-parts":[[2020,5,29]],"date-time":"2020-05-29T10:02:27Z","timestamp":1590746547000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["CYP17A1 deficient XY mice display susceptibility to atherosclerosis, altered lipidomic profile and atypical sex development"],"prefix":"10.1038","volume":"10","author":[{"given":"Redouane","family":"Aherrahrou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra E.","family":"Kulle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6071-5433","authenticated-orcid":false,"given":"Natalia","family":"Alenina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3718-3595","authenticated-orcid":false,"given":"Ralf","family":"Werner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4773-4653","authenticated-orcid":false,"given":"Simeon","family":"Vens-Cappell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bader","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heribert","family":"Schunkert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4486-6231","authenticated-orcid":false,"given":"Jeanette","family":"Erdmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zouhair","family":"Aherrahrou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"65601_CR1","first-page":"e38","volume":"133","author":"D Mozaffarian","year":"2016","unstructured":"Mozaffarian, D. et al. 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