{"doi":"10.1172/jci.insight.190105","title":"Development and characterization of an Sf-1-Flp mouse model","abstract":"The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enables the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons (Sf-1-Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH. Here, we developed and characterized Sf-1-Flp mice and demonstrated their utility. The Flp sequence was inserted into the Sf-1 locus with P2A. This insertion did not affect Sf-1 mRNA expression levels and Sf-1-Flp mice do not have any visible phenotypes. They are fertile and metabolically comparable to wild-type littermate mice. Optogenetic stimulation using adeno-associated virus (AAV) carrying Flp-dependent channelrhodopsin-2 (ChR2) increased blood glucose and skeletal muscle PGC-1α in Sf-1-Flp mice. This was similar to SF-1 neuronal activation using Sf-1-BAC-Cre and AAV carrying Cre-dependent ChR2. Finally, we generated Sf-1-Flp mice that lack β2-adrenergic receptors (Adrb2) only in skeletal muscle with a combination of Cre/LoxP technology (Sf-1-Flp:SKMΔAdrb2). Optogenetic stimulation of SF-1 neurons failed to increase skeletal muscle PGC-1α in Sf-1-Flp:SKMΔAdrb2 mice, suggesting that Adrb2 in skeletal muscle is required for augmented skeletal muscle PGC-1α by SF-1 neuronal activation. Our data demonstrate that Sf-1-Flp mice are useful for interrogating complex physiology.","journal":"JCI Insight","year":2025,"id":543297,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1433368,"name":"Mina Fujitani","orcid":null,"position":1,"is_corresponding":false},{"id":1250554,"name":"Samuel R. Heaselgrave","orcid":null,"position":2,"is_corresponding":false},{"id":1433369,"name":"Shreya Thomas","orcid":null,"position":3,"is_corresponding":false},{"id":1201533,"name":"Bandy Chen","orcid":"0009-0009-9099-1218","position":4,"is_corresponding":false},{"id":704025,"name":"Jenny J. Lee","orcid":null,"position":5,"is_corresponding":false},{"id":366032,"name":"Steven C. Wyler","orcid":"0000-0003-1748-0525","position":6,"is_corresponding":false},{"id":292392,"name":"Joel K. Elmquist","orcid":"0000-0001-6929-6370","position":7,"is_corresponding":false},{"id":384725,"name":"Teppei Fujikawa","orcid":"0000-0002-4056-0526","position":8,"is_corresponding":false},{"id":1433367,"name":"Marco Galvan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:53:04.088079Z","pmid":"40036073","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":[]}