{"doi":"10.1002/brb3.70239","title":"Aldh1l1‐Cre/ERT2 Drives Flox‐Mediated Recombination in Peripheral and CNS Infiltrating Immune Cells in Addition to Astrocytes During CNS Autoimmune Disease","abstract":"INTRODUCTION: The transgenic murine Cre/loxP system is deployed to investigate the role of central nervous system (CNS) cell-specific gene alterations in both healthy conditions and models of neurologic disease. The Aldh1l1-Cre/ERT2 line is widely used to target astrocytes with high coverage and specificity within the CNS. Specificity outside the CNS, however, has not been well-characterized, and Aldh1l1-Cre/ERT2-mediated recombination within the spleen has been reported. In many CNS diseases, infiltrating immune cells from the periphery drive or regulate pathogenesis. We tested whether flox-mediated recombination from Aldh1l1-Cre/ERT2 occurs in immune cells in addition to astrocytes and whether these cells traffic from the spleen into the spinal cord during experimental autoimmune encephalomyelitis (EAE), a model of CNS autoimmune disease. METHODS: Two astrocyte-targeted mouse lines were generated with the red fluorescent reporter, tdTomato, by crossing the Cre-recombinase lines, Tg(Aldh1l1-Cre/ERT2)1Khakh and Tg(Gfap-Cre)73.12Mvs, with the reporter line, Gt(ROSA)26Sor. Aldh1l1-Cre/ERT2 was activated with 5 days of intraperitoneal tamoxifen, whereas Gfap-Cre was constitutively active. EAE was induced 2 weeks after tamoxifen, and then spleens and spinal cords were harvested and processed for flow cytometry at various time points after disease onset in EAE versus healthy controls. RESULTS: T cells. CONCLUSION: Use of Aldh1l1-Cre/ERT2 should therefore account for recombination in both astrocytes and immune cells in disease models involving peripheral immune cell infiltration into the CNS.","journal":"Brain and Behavior","year":2025,"id":522675,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"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":1394157,"name":"Juan Turati","orcid":"0000-0003-3817-0489","position":1,"is_corresponding":false},{"id":1394809,"name":"Josh Weiss","orcid":null,"position":2,"is_corresponding":false},{"id":938974,"name":"Jorge Villavicencio","orcid":"0009-0001-1246-2857","position":3,"is_corresponding":false},{"id":305849,"name":"Zhihong Chen","orcid":"0000-0001-7403-7015","position":4,"is_corresponding":false},{"id":105214,"name":"Graham J. Britton","orcid":"0000-0003-4630-1223","position":5,"is_corresponding":false},{"id":723575,"name":"Sam Horng","orcid":"0000-0001-5391-9000","position":6,"is_corresponding":false},{"id":638392,"name":"Mario Amatruda","orcid":"0000-0002-5407-238X","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:49:54.058858Z","pmid":"39910805","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":[]}