{"doi":"10.1172/jci.insight.178993","title":"Gα11 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia","abstract":"Fibroblast growth factor 23 (FGF23) production has recently been shown to increase downstream of Gαq/11-PKC signaling in osteocytes. Inactivating mutations in the gene encoding Gα11 (GNA11) cause familial hypocalciuric hypercalcemia (FHH) due to impaired calcium-sensing receptor signaling. We explored the effect of Gα11 deficiency on FGF23 production in mice with heterozygous (Gna11+/-) or homozygous (Gna11-/-) ablation of Gna11. Both Gna11+/- and Gna11-/- 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. Gna11-/- mice showed augmented Fgf23 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-1β levels. Furin gene expression was significantly increased in the Gna11-/- liver, suggesting enhanced FGF23 cleavage despite the observed rise in circulating intact FGF23 levels. Gna11-/- 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, Gα11 ablation caused systemic inflammation and excess serum FGF23 in mice, suggesting that patients with FHH - at least those with GNA11 mutations - may be at risk for these complications.","journal":"JCI Insight","year":2024,"id":476595,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9564,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1264357,"name":"Sajin Marcus Cyr","orcid":null,"position":1,"is_corresponding":false},{"id":1264358,"name":"Kaitlin Klovdahl","orcid":null,"position":2,"is_corresponding":false},{"id":268742,"name":"Wen Zhou","orcid":"0000-0001-8455-6011","position":3,"is_corresponding":false},{"id":311848,"name":"Christina M. Tognoni","orcid":"0000-0001-5073-8693","position":4,"is_corresponding":false},{"id":789811,"name":"Yorihiro Iwasaki","orcid":"0000-0001-9787-7922","position":5,"is_corresponding":false},{"id":268754,"name":"Eugene P. Rhee","orcid":"0000-0002-4804-7583","position":6,"is_corresponding":false},{"id":311853,"name":"Alpaslan Dedeoglu","orcid":"0000-0003-1156-0874","position":7,"is_corresponding":false},{"id":268740,"name":"Petra Šimić","orcid":"0000-0002-5958-8561","position":8,"is_corresponding":false},{"id":780085,"name":"Murat Bastepe","orcid":"0000-0002-2643-3504","position":9,"is_corresponding":false},{"id":780080,"name":"Birol Ay","orcid":"0000-0001-9505-4658","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-19T02:06:29.605760Z","pmid":"38530370","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}