{"doi":"10.1172/jci.insight.146604","title":"An inducible Cre mouse for studying roles of the RPE in retinal physiology and disease","abstract":"The retinal pigment epithelium (RPE) provides vital metabolic support for retinal photoreceptor cells and is an important player in numerous retinal diseases. Gene manipulation in mice using the Cre-LoxP system is an invaluable tool for studying the genetic basis of these retinal diseases. However, existing RPE-targeted Cre mouse lines have critical limitations that restrict their reliability for studies of disease pathogenesis and treatment, including mosaic Cre expression, inducer-independent activity, off-target Cre expression, and intrinsic toxicity. Here, we report the generation and characterization of a knockin mouse line in which a P2A-CreERT2 coding sequence is fused with the native RPE-specific 65 kDa protein (Rpe65) gene for cotranslational expression of CreERT2. Cre+/- mice were able to recombine a stringent Cre reporter allele with more than 99% efficiency and absolute RPE specificity upon tamoxifen induction at both postnatal days (PD) 21 and 50. Tamoxifen-independent Cre activity was negligible at PD64. Moreover, tamoxifen-treated Cre+/- mice displayed no signs of structural or functional retinal pathology up to 4 months of age. Despite weak RPE65 expression from the knockin allele, visual cycle function was normal in Cre+/- mice. These data indicate that Rpe65CreERT2 mice are well suited for studies of gene function and pathophysiology in the RPE.","journal":"JCI Insight","year":2021,"id":160290,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254236,"name":"Susie Suh","orcid":"0000-0002-4921-1429","position":1,"is_corresponding":false},{"id":672762,"name":"David E. Einstein","orcid":"0000-0003-1584-4049","position":2,"is_corresponding":false},{"id":254238,"name":"Henri Leinonen","orcid":"0000-0002-0388-832X","position":3,"is_corresponding":false},{"id":254241,"name":"Zhiqian Dong","orcid":"0000-0002-8748-4532","position":4,"is_corresponding":false},{"id":415860,"name":"Sriganesh Ramachandra Rao","orcid":"0000-0003-1029-1051","position":5,"is_corresponding":false},{"id":415861,"name":"Steven J. Fliesler","orcid":"0000-0002-2557-142X","position":6,"is_corresponding":false},{"id":245623,"name":"Seth Blackshaw","orcid":"0000-0002-1338-8476","position":7,"is_corresponding":false},{"id":672763,"name":"Minzhong Yu","orcid":"0000-0002-3115-8930","position":8,"is_corresponding":false},{"id":54616,"name":"Neal S. Peachey","orcid":"0000-0002-4419-7226","position":9,"is_corresponding":false},{"id":254244,"name":"Krzysztof Palczewski","orcid":"0000-0002-0788-545X","position":10,"is_corresponding":false},{"id":254242,"name":"Philip D. Kiser","orcid":"0000-0003-1184-9539","position":11,"is_corresponding":false},{"id":254237,"name":"Elliot H. Choi","orcid":"0000-0001-8762-5473","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-18T23:44:43.908634Z","pmid":"33784255","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":[]}