{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:08:54Z","timestamp":1791857334501,"version":"4.3.4"},"reference-count":44,"publisher":"American Society for Clinical Investigation","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,2,9]]},"abstract":"<jats:p>\n                    Heterotrimeric G proteins play critical roles in transducing extracellular signals generated by 7-transmembrane domain receptors. Somatic gain-of-function mutations in G protein \u03b1 subunits are associated with a variety of diseases. Recently, we identified gain-of-function mutations in G\u03b1\n                    <jats:sub>11<\/jats:sub>\n                    in patients with autosomal-dominant hypocalcemia type 2 (ADH2), an inherited disorder of hypocalcemia, low parathyroid hormone (PTH), and hyperphosphatemia. We have generated knockin mice harboring the point mutation\n                    <jats:italic>GNA11<\/jats:italic>\n                    c.C178T (p.Arg60Cys) identified in ADH2 patients. The mutant mice faithfully replicated human ADH2. They also exhibited low bone mineral density and increased skin pigmentation. Treatment with NPS 2143, a negative allosteric modulator of the calcium-sensing receptor (CASR), increased PTH and calcium concentrations in WT and mutant mice, suggesting that the gain-of-function effect of GNA11\n                    <jats:sup>R6OC<\/jats:sup>\n                    is partly dependent on coupling to the CASR. Treatment with the G\u03b1\n                    <jats:sub>11\/q<\/jats:sub>\n                    -specific inhibitor YM-254890 increased blood calcium in heterozygous but not in homozygous\n                    <jats:italic>GNA11<\/jats:italic>\n                    <jats:sup>R60C<\/jats:sup>\n                    mice, consistent with published crystal structure data showing that Arg60 forms a critical contact with YM-254890. This animal model of ADH2 provides insights into molecular mechanism of this G protein\u2013related disease and potential paths toward new lines of therapy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.91079","type":"journal-article","created":{"date-parts":[[2017,2,8]],"date-time":"2017-02-08T11:00:49Z","timestamp":1486551649000},"source":"Crossref","is-referenced-by-count":33,"title":["Knockin mouse with mutant G\u03b111 mimics human inherited hypocalcemia and is rescued by pharmacologic inhibitors"],"prefix":"10.1172","volume":"2","author":[{"given":"Kelly L.","family":"Roszko","sequence":"first","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiye","family":"Bi","sequence":"additional","affiliation":[{"name":"Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA."},{"name":"West 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