{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:16:41Z","timestamp":1784557001088,"version":"3.55.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,2]]},"abstract":"\n Hypoparathyroidism is genetically heterogeneous and characterized by low plasma calcium and parathyroid hormone (PTH) concentrations. X-linked hypoparathyroidism (XLHPT) in two American families is associated with interstitial deletion-insertions involving deletions of chromosome Xq27.1 downstream of\n SOX3<\/jats:italic>\n and insertions of predominantly non-coding DNA from chromosome 2p25.3. These could result in loss, gain, or movement of regulatory elements, which include ultraconserved element\n uc482<\/jats:italic>\n , which could alter\n SOX3<\/jats:italic>\n expression. To investigate this, we analysed\n SOX3<\/jats:italic>\n expression in EBV-transformed lymphoblastoid cells from three affected males, three unaffected males, and four carrier females from one XLHPT family. SOX3 expression was similar in all individuals, indicating that the spatiotemporal effect of the interstitial deletion-insertion on SOX3 expression postulated to occur in developing parathyroids did not manifest in lymphoblastoids. Expression of\n SNTG2<\/jats:italic>\n , which is duplicated and inserted into the X chromosome, and\n ATP11C<\/jats:italic>\n , which is moved telomerically, were also similarly expressed in all individuals. Investigation of male hemizygous (\n Sox3<\/jats:italic>\n \u2212\/Y<\/jats:sup>\n and\n uc482<\/jats:italic>\n \u2212\/Y<\/jats:sup>\n ) and female heterozygous (\n Sox3<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n and\n uc482<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n ) knockout mice, together with wild-type littermates (male\n Sox3<\/jats:italic>\n +\/Y<\/jats:sup>\n and\n uc482<\/jats:italic>\n +\/Y<\/jats:sup>\n , and female\n Sox3<\/jats:italic>\n +\/+<\/jats:sup>\n and\n uc482<\/jats:italic>\n +\/+<\/jats:sup>\n ), revealed\n Sox3<\/jats:italic>\n \u2212\/Y<\/jats:sup>\n ,\n Sox3<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n ,\n uc482<\/jats:italic>\n \u2212<\/jats:sup>\n \/Y, and\n uc482<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n mice to have normal plasma biochemistry, compared to their respective wild-type littermates. When challenged with a low calcium diet, all mice had hypocalcaemia, and elevated plasma PTH concentrations and alkaline phosphatase activities, and\n Sox3<\/jats:italic>\n \u2212\/Y<\/jats:sup>\n ,\n Sox3<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n ,\n uc482<\/jats:italic>\n \u2212\/Y<\/jats:sup>\n , and\n uc482<\/jats:italic>\n +\/<\/jats:sup>\n \u2212<\/jats:sup>\n mice had similar plasma biochemistry, compared to wild-type littermates. Thus, these results indicate that absence of\n Sox3<\/jats:italic>\n or\n uc482<\/jats:italic>\n does not cause hypoparathyroidism and that XLHPT likely reflects a more complex mechanism.\n <\/jats:p>","DOI":"10.1530\/ec-19-0478","type":"journal-article","created":{"date-parts":[[2020,1,28]],"date-time":"2020-01-28T10:18:09Z","timestamp":1580206689000},"page":"173-186","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":8,"title":["Studies of mice deleted for Sox3 and uc482: relevance to X-linked hypoparathyroidism"],"prefix":"10.1530","volume":"9","author":[{"given":"Katherine U","family":"Gaynor","sequence":"first","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina V","family":"Grigorieva","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha M","family":"Mirczuk","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sian E","family":"Piret","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kreepa G","family":"Kooblall","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Stevenson","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Rizzoti","sequence":"additional","affiliation":[{"name":"2The Francis Crick Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Bowl","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Andrew","family":"Nesbit","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul T","family":"Christie","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D","family":"Fraser","sequence":"additional","affiliation":[{"name":"3Norwich Medical School, Faculty of Medicine and Health Sciences, University of East Anglia, Norwich, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tertius","family":"Hough","sequence":"additional","affiliation":[{"name":"4MRC Mammalian Genetics Unit, MRC Harwell Institute, Harwell Science and Innovation Campus, Oxfordshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P","family":"Whyte","sequence":"additional","affiliation":[{"name":"5Washington University in St Louis School of Medicine, Center for Metabolic Bone Disease and Molecular Research, St Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Lovell-Badge","sequence":"additional","affiliation":[{"name":"2The Francis Crick Institute, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajesh V","family":"Thakker","sequence":"additional","affiliation":[{"name":"1Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/9\/2\/EC-19-0478.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/9\/2\/EC-19-0478.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:43:48Z","timestamp":1784555028000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/9\/2\/173-186\/635"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/ec-19-0478","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,2]]}}}