{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T03:00:47Z","timestamp":1785121247485,"version":"3.55.0"},"reference-count":45,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2020\u201004366"],"award-info":[{"award-number":["2020\u201004366"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["233384"],"award-info":[{"award-number":["233384"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002808","name":"Carlsbergfondet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002808","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004836","name":"Danmarks Frie Forskningsfond","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004836","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Transepithelial calcium absorption occurs via a transcellular or paracellular pathway. The intestinal transcellular pathway relies, at least partially, on the apical calcium channel transient receptor potential vanilloid 6 (TRPV6), whereas paracellular calcium (re)absorption occurs through tight junction proteins, including claudin\u20102 (CLDN2). Both CLDN2 and TRPV6 are also expressed in the kidney. CLDN2 contributes to proximal tubular calcium reabsorption, whereas the functional relevance of TRPV6 remains unclear.\n                    <jats:italic>Cldn2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    knockout mice exhibit reduced intestinal calcium permeability and hypercalciuria, while maintaining normal bone mineral density (BMD), plasma calcium, and calciotropic hormone levels.\n                    <jats:italic>Trpv6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>D541A\/D541A<\/jats:italic>\n                    <\/jats:sup>\n                    pore mutants were reported to have normal urinary and plasma calcium levels, despite reduced intestinal calcium absorption on a low calcium diet. However, we found subtle sex\u2010specific differences in calcium homeostasis in these mice. We hypothesized that transcellular and paracellular calcium absorption pathways compensate for one another in these models. To test this, we crossed\n                    <jats:italic>Cldn2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    with\n                    <jats:italic>Trpv6<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>D541A\/D541A<\/jats:italic>\n                    <\/jats:sup>\n                    mice to generate a functional double knockout (DKO,\n                    <jats:italic>Cldn2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    \/\n                    <jats:italic>Trpv6<\/jats:italic>\n                    <jats:sup>D541A\/D541A<\/jats:sup>\n                    ). These mice displayed hypocalcemia, elevated calcitriol, and reduced BMD. Surprisingly, despite unchanged fecal calcium excretion, renal calcium wasting was greater than in\n                    <jats:italic>Cldn2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice. Gene expression studies revealed increased calbindin\u2010D\n                    <jats:sub>9k<\/jats:sub>\n                    expression in the proximal colon and calbindin\u2010D\n                    <jats:sub>28k<\/jats:sub>\n                    in the kidney, consistent with partial compensation by the colon and distal nephron. Together, these findings indicate that combined impairment of paracellular and transcellular calcium transport reduces intestinal and renal calcium (re)absorption, leading to hypocalcemia and increased calcitriol levels, and highlight a role for TRPV6 in distal nephron calcium handling.\n                  <\/jats:p>","DOI":"10.1111\/apha.70279","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:43:47Z","timestamp":1784616227000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of\n                    <i>Claudin\u20102<\/i>\n                    and\n                    <i>Trpv6<\/i>\n                    Results in Hypocalcemia, Hypercalciuria, and Altered Bone Microarchitecture in Mice"],"prefix":"10.1111","volume":"242","author":[{"given":"Harneet Kaur","family":"Bhullar","sequence":"first","affiliation":[{"name":"Department of Physiology University of Alberta  Edmonton Alberta Canada"},{"name":"Women's and Children's Health Institute  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda Lima","family":"Deluque","sequence":"additional","affiliation":[{"name":"Women's and Children's Health Institute  Edmonton Alberta Canada"},{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debbie D.","family":"O'Neil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanling","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Doschak","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta  Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9170-2168","authenticated-orcid":false,"given":"Henrik","family":"Dimke","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Renal Research, Institute of Molecular Medicine University of Southern Denmark  Odense Denmark"},{"name":"Department of Nephrology Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Todd","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Alberta  Edmonton Alberta Canada"},{"name":"Women's and Children's Health Institute  Edmonton Alberta Canada"},{"name":"Department of Pediatrics University of Alberta  Edmonton Alberta Canada"},{"name":"Department of Cardiovascular and Renal Research, Institute of Molecular Medicine University of Southern Denmark  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.05910809"},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","unstructured":"J. G. J.Hoenderop B.Nilius andR. J. 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