{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:41:47Z","timestamp":1791297707590,"version":"4.1.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2007,2,1]],"date-time":"2007-02-01T00:00:00Z","timestamp":1170288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We report the phenotype of mice with targeted disruption of the Trpv6 (Trpv6 KO) epithelial calcium channel. The mice exhibit disordered Ca2+ homeostasis, including defective intestinal Ca2+ absorption, increased urinary Ca2+ excretion, decreased BMD, deficient weight gain, and reduced fertility. Although our Trpv6 KO affects the closely adjacent EphB6 gene, the phenotype reported here is not related to EphB6 dysfunction.<\/jats:p>\n               <jats:p>Introduction: The mechanisms underlying intestinal Ca2+ absorption are crucial for overall Ca2+ homeostasis, because diet is the only source of all new Ca2+ in the body. Trpv6 encodes a Ca2+-permeable cation channel responsible for vitamin D\u2013dependent intestinal Ca2+ absorption. Trpv6 is expressed in the intestine and also in the skin, placenta, kidney, and exocrine organs.<\/jats:p>\n               <jats:p>Materials and Methods: To determine the in vivo function of TRPV6, we generated mice with targeted disruption of the Trpv6 (Trpv6 KO) gene.<\/jats:p>\n               <jats:p>Results: Trpv6 KO mice are viable but exhibit disordered Ca2+ homeostasis, including a 60% decrease in intestinal Ca2+ absorption, deficient weight gain, decreased BMD, and reduced fertility. When kept on a regular (1% Ca2+) diet, Trpv6 KO mice have deficient intestinal Ca2+ absorption, despite elevated levels of serum PTH (3.8-fold) and 1,25-dihydroxyvitamin D (2.4-fold). They also have decreased urinary osmolality and increased Ca2+ excretion. Their serum Ca2+ is normal, but when challenged with a low (0.25%) Ca2+ diet, Trpv6 KO mice fail to further increase serum PTH and vitamin D, ultimately developing hypocalcemia. Trpv6 KO mice have normal urinary deoxypyridinoline excretion, although exhibiting a 9.3% reduction in femoral mineral density at 2 months of age, which is not restored by treatment for 1 month with a high (2%) Ca2+ \u201crescue\u201d diet. In addition to their deranged Ca2+ homeostasis, the skin of Trpv6 KO mice has fewer and thinner layers of stratum corneum, decreased total Ca2+ content, and loss of the normal Ca2+ gradient. Twenty percent of all Trpv6 KO animals develop alopecia and dermatitis.<\/jats:p>\n               <jats:p>Conclusions: Trpv6 KO mice exhibit an array of abnormalities in multiple tissues\/organs. At least some of these are caused by tissue-specific mechanisms. In addition, the kidneys and bones of Trpv6 KO mice do not respond to their elevated levels of PTH and 1,25-dihydroxyvitamin D. These data indicate that the TRPV6 channel plays an important role in Ca2+ homeostasis and in other tissues not directly involved in this process.<\/jats:p>","DOI":"10.1359\/jbmr.061110","type":"journal-article","created":{"date-parts":[[2006,11,27]],"date-time":"2006-11-27T19:24:03Z","timestamp":1164655443000},"page":"274-285","source":"Crossref","is-referenced-by-count":259,"title":["Marked Disturbance of Calcium Homeostasis in Mice With Targeted Disruption of the <i>Trpv6<\/i> Calcium Channel Gene"],"prefix":"10.1093","volume":"22","author":[{"given":"Suzy DC","family":"Bianco","sequence":"first","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Bin","family":"Peng","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Takanaga","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine H","family":"Kos","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Urological Diseases Research Center, Children's Hospital & Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Freeman","sequence":"additional","affiliation":[{"name":"Urological Diseases Research Center, Children's Hospital & Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia HA","family":"Gouveia","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangping","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Centre de Recherche, Centre Hospitalier de I'Universite de Montreal, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Luo","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology, Centre de Recherche, Centre Hospitalier de I'Universite de Montreal, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodora","family":"Mauro","sequence":"additional","affiliation":[{"name":"Department of Dermatology, UCSF, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward M","family":"Brown","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias A","family":"Hediger","sequence":"additional","affiliation":[{"name":"Membrane Biology Program and Renal 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