{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T18:12:18Z","timestamp":1791137538323,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,12,3]],"date-time":"2002-12-03T00:00:00Z","timestamp":1038873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011747","name":"Novo Nordisk Foundation Center for Basic Metabolic Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011747","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2003,2]]},"abstract":"<jats:p>\n                    Megalin is an endocytic receptor highly expressed in the proximal tubules of the kidney. Recently, we demonstrated that this receptor is essential for the renal uptake and conversion of 25\u2010OH vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    to 1,25\u2010(OH)\n                    <jats:sub>2<\/jats:sub>\n                    vitamin D\n                    <jats:sub>3<\/jats:sub>\n                    , a central step in vitamin D and bone metabolism. Unfortunately, the perinatal lethality of the conventional megalin knockout mouse model precluded the detailed analysis of the significance of megalin for calcium homeostasis and bone turnover\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we have generated a new mouse model with conditional inactivation of the megalin gene in the kidney by using Cre recombinase. Animals with a renal\u2010specific receptor gene defect were viable and fertile. However, lack of receptor expression in the kidney results in plasma vitamin D deficiency, in hypocalcemia and in severe bone disease, characterized by a decrease in bone mineral content, an increase in osteoid surfaces, and a lack of mineralizing activity. These features are consistent with osteomalacia (softening of the bones) as a consequence of hypovitaminosis D and demonstrate the crucial importance of the megalin pathway for systemic calcium homeostasis and bone metabolism.\n                  <\/jats:p>","DOI":"10.1096\/fj.02-0578fje","type":"journal-article","created":{"date-parts":[[2003,1,28]],"date-time":"2003-01-28T17:25:55Z","timestamp":1043774755000},"page":"247-249","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":152,"title":["Hypocalcemia and osteopathy in mice with kidney\u2010specific megalin gene defect"],"prefix":"10.1096","volume":"17","author":[{"given":"J\u00f6rg R.","family":"Leheste","sequence":"first","affiliation":[{"name":"Max\u2010Delbrueck\u2010Center for Molecular Medicine Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flemming","family":"Melsen","sequence":"additional","affiliation":[{"name":"Department of Pathology Aarhus University Hospital Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maren","family":"Wellner","sequence":"additional","affiliation":[{"name":"Franz\u2010Volhard\u2010Clinic Humboldt University of Berlin Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pernille","family":"Jansen","sequence":"additional","affiliation":[{"name":"Departments of Medical Biochemistry Connective Tissue Biology University of Aarhus Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Schlichting","sequence":"additional","affiliation":[{"name":"Institute for Anatomy Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Renner\u2010M\u00fcller","sequence":"additional","affiliation":[{"name":"Gene Center Ludwig\u2010Maximilians\u2010University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troels T.","family":"Andreassen","sequence":"additional","affiliation":[{"name":"Departments of Medical Biochemistry Connective Tissue Biology University of Aarhus Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckehard","family":"Wolf","sequence":"additional","affiliation":[{"name":"Gene Center Ludwig\u2010Maximilians\u2010University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bachmann","sequence":"additional","affiliation":[{"name":"Institute for Anatomy Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Nykjaer","sequence":"additional","affiliation":[{"name":"Gene Center Ludwig\u2010Maximilians\u2010University Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Willnow","sequence":"additional","affiliation":[{"name":"Max\u2010Delbrueck\u2010Center for Molecular Medicine Berlin"},{"name":"Medical Faculty of the Free University of Berlin Berlin"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,12,3]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.157.2.667"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.9725"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V10102224"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V104685"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80655-8"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00206.2000"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65238-8"},{"key":"e_1_2_6_9_1","first-page":"1","article-title":"Plasma vitamin D\u2010binding protein (Gc\u2010globulin): Multiple tasks","volume":"53","author":"Haddad J. G.","year":"1995","journal-title":"J. Steroid Biochem."},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-2712(18)30054-4"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.1976.tb03819.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200206000-00004"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI5244"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.16.8460"},{"key":"e_1_2_6_15_1","doi-asserted-by":"crossref","DOI":"10.1046\/j.1523-1755.2002.00634.x","article-title":"Expression profiling confirms role of endocytic receptor megalin in renal vitamin D metabolism","author":"Hilpert J.","year":"2002","journal-title":"Kidney Int."},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.241516998"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(78)91322-0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V12112209"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8016642"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-10-3-232"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(00)00317-9"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00966.x"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.2.888"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118176"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109959200"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.25.17518"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0132u.x"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M000955200"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1681\/ASN.V11122167","article-title":"Characterization of ANKRA, a novel ankyrin repeat protein that interacts with the cytoplasmic domain of megalin","volume":"11","author":"Rader K.","year":"2001","journal-title":"J. Am. Soc. Nephrol."},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3470613"},{"key":"e_1_2_6_31_1","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1681\/ASN.V124667","article-title":"The membrane\u2010associated guanylate kinase protein MAGI\u20101 binds megalin and is present in glomerular podocytes","volume":"12","author":"Patrie K. M.","year":"2001","journal-title":"J. Am. Soc. Nephrol."}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.02-0578fje","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.02-0578fje","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.02-0578fje","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T20:43:28Z","timestamp":1761684208000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.02-0578fje"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,12,3]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2003,2]]}},"alternative-id":["10.1096\/fj.02-0578fje"],"URL":"https:\/\/doi.org\/10.1096\/fj.02-0578fje","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,12,3]]},"assertion":[{"value":"2002-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-10-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-12-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}