{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:13:02Z","timestamp":1779142382182,"version":"3.51.4"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"9","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01DK121776"],"award-info":[{"award-number":["R01DK121776"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30 AR075042"],"award-info":[{"award-number":["P30 AR075042"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,8]]},"abstract":"<jats:p>\n                    Fibroblast growth factor 23 (FGF23) production has recently been shown to increase downstream of G\u03b1\n                    <jats:sub>q\/11<\/jats:sub>\n                    -PKC signaling in osteocytes. Inactivating mutations in the gene encoding G\u03b1\n                    <jats:sub>11<\/jats:sub>\n                    (\n                    <jats:italic>GNA11<\/jats:italic>\n                    ) cause familial hypocalciuric hypercalcemia (FHH) due to impaired calcium-sensing receptor signaling. We explored the effect of G\u03b1\n                    <jats:sub>11<\/jats:sub>\n                    deficiency on FGF23 production in mice with heterozygous (\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    ) or homozygous (\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) ablation of\n                    <jats:italic>Gna11<\/jats:italic>\n                    . Both\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>+\/\u2013<\/jats:sup>\n                    and\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice demonstrated hypercalcemia and mildly raised parathyroid hormone levels, consistent with FHH. Strikingly, these mice also displayed increased serum levels of total and intact FGF23 and hypophosphatemia.\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice showed augmented\n                    <jats:italic>Fgf23<\/jats:italic>\n                    mRNA levels in the liver and heart, but not in bone or bone marrow, and also showed evidence of systemic inflammation with elevated serum IL-1\u03b2 levels.\n                    <jats:italic>Furin<\/jats:italic>\n                    gene expression was significantly increased in the\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    liver, suggesting enhanced FGF23 cleavage despite the observed rise in circulating intact FGF23 levels.\n                    <jats:italic>Gna11<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice had normal renal function and reduced serum levels of glycerol-3-phosphate, excluding kidney injury as the primary cause of elevated intact FGF23 levels. Thus, G\u03b1\n                    <jats:sub>11<\/jats:sub>\n                    ablation caused systemic inflammation and excess serum FGF23 in mice, suggesting that patients with FHH \u2014 at least those with\n                    <jats:italic>GNA11<\/jats:italic>\n                    mutations \u2014 may be at risk for these complications.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.178993","type":"journal-article","created":{"date-parts":[[2024,4,5]],"date-time":"2024-04-05T08:42:58Z","timestamp":1712306578000},"source":"Crossref","is-referenced-by-count":2,"title":["G\u03b111 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia"],"prefix":"10.1172","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9505-4658","authenticated-orcid":true,"given":"Birol","family":"Ay","sequence":"first","affiliation":[{"name":"Endocrine Unit, Department of Medicine, 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