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Here, we describe a novel <jats:italic>in vivo<\/jats:italic> system using genetically modified rats deficient in the <jats:italic>Cyp27b1<\/jats:italic> or <jats:italic>Vdr<\/jats:italic> genes. Type II rickets model rats with a mutant <jats:italic>Vdr<\/jats:italic> (R270L), which recognizes 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> with an affinity equivalent to that for 25(OH)D<jats:sub>3<\/jats:sub>, were also generated. Although <jats:italic>Cyp27b1<\/jats:italic>-knockout (KO), <jats:italic>Vdr-<\/jats:italic>KO, and <jats:italic>Vdr<\/jats:italic> (R270L) rats each showed rickets symptoms, including abnormal bone formation, they were significantly different from each other. Administration of 25(OH)D<jats:sub>3<\/jats:sub> reversed rickets symptoms in <jats:italic>Cyp27b1<\/jats:italic>-KO and <jats:italic>Vdr<\/jats:italic> (R270L) rats. Interestingly, 1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub> was synthesized in <jats:italic>Cyp27b1<\/jats:italic>-KO rats, probably by Cyp27a1. In contrast, the effects of 25(OH)D<jats:sub>3<\/jats:sub> on <jats:italic>Vdr<\/jats:italic> (R270L) rats strongly suggested a direct action of 25(OH)D<jats:sub>3<\/jats:sub> via VDR-genomic pathways. These results convincingly suggest the usefulness of our <jats:italic>in vivo<\/jats:italic> system.<\/jats:p>","DOI":"10.1038\/s41598-020-62048-1","type":"journal-article","created":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T10:03:55Z","timestamp":1585562635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Generation of novel genetically modified rats to reveal the molecular mechanisms of vitamin D actions"],"prefix":"10.1038","volume":"10","author":[{"given":"Miyu","family":"Nishikawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Takamatsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Abe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kairi","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyohei","family":"Horibe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Mano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimie","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoko","family":"Tsugawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6462-9479","authenticated-orcid":false,"given":"Yoshihisa","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2095-9425","authenticated-orcid":false,"given":"Tetsuhiro","family":"Horie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiichi","family":"Hinoi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshio","family":"Okano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Ikushiro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Sakaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"62048_CR1","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/nrd3318","volume":"9","author":"LA Plum","year":"2010","unstructured":"Plum, L. 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