{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:25:40Z","timestamp":1781101540010,"version":"3.54.1"},"reference-count":59,"publisher":"National Academy of Sciences","issue":"1","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,1,3]]},"abstract":"<jats:p>\n                    The hormonally active form of vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    ,1\u03b1,25-dihydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    [1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    ], is synthesized in the kidney through a tightly regulated reaction catalyzed by 25-hydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    -1\u03b1-hydroxylase (1\u03b1-hydroxylase), the product of the\n                    <jats:italic>CYP27B1<\/jats:italic>\n                    gene. Through gene targeting in embryonic stem cells, we engineered a mouse strain in which the coding region of the 1\u03b1-hydroxylase gene is replaced by the genes for \u03b2-galactosidase (\n                    <jats:italic>lacZ<\/jats:italic>\n                    ) and neomycin resistance. Null mice produced no detectable 1\u03b1-hydroxylase transcript. The mice grew normally when maintained on a balanced diet containing 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    but rapidly developed rickets when phosphorus and 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    were restricted. Rickets was curable through administration of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    but not its biological precursor, 25-hydroxyvitamin D\n                    <jats:sub>3<\/jats:sub>\n                    . Upon administration of a diet low in calcium and devoid of any form of vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , \u03b2-galactosidase activity was detected in the kidneys of the \u2013\/\u2013 and +\/\u2013 mice and in placentas harvested from \u2013\/\u2013 females bred with \u2013\/\u2013 males. No \u03b2-galactosidase activity was detected in skin sections or in primary keratinocyte cultures from \u2013\/\u2013 animals. Our results demonstrate we have generated 1\u03b1-hydroxylase null mice that display phenotypes characteristic of vitamin D-dependency rickets type I. From the histochemical analysis of reporter gene expression in these mice, we conclude that acute 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    deficiency in otherwise healthy animals does not stimulate local production of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    in the skin. These findings stand in contrast to previously published reports of 1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    production in keratinocytes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0509734103","type":"journal-article","created":{"date-parts":[[2005,12,21]],"date-time":"2005-12-21T20:34:25Z","timestamp":1135197265000},"page":"75-80","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":67,"title":["CYP27B1 null mice with\n                    <i>LacZ<\/i>\n                    reporter gene display no 25-hydroxyvitamin D\n                    <sub>3<\/sub>\n                    -1\u03b1-hydroxylase promoter activity in the skin"],"prefix":"10.1073","volume":"103","author":[{"given":"Janeen L.","family":"Vanhooke","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean M.","family":"Prahl","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Kimmel-Jehan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Mendelsohn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric W.","family":"Danielson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Healy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector F.","family":"DeLuca","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Wisconsin, Madison, WI 53706; and Center for Neurobiology and Behavior, Columbia University, New York, NY 10032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,12,21]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1998.78.4.1193"},{"key":"e_1_3_2_2_2","first-page":"1961","volume":"11","year":"1997","unstructured":"Fu, G. 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