{"doi":"10.1111/febs.70328","title":"Conditional deletion of the multiple sclerosis susceptibility gene <scp> <i>ATXN1</i> </scp> identifies cell‐autonomous effects in the B‐cell compartment","abstract":"Increasing evidence supports a mechanistic role for B cells in the pathogenesis of the autoimmune disorder multiple sclerosis (MS). We previously documented that the MS risk gene ataxin-1 (ATXN1) modulates key B-cell functions and the severity of the MS disease model experimental autoimmune encephalomyelitis (EAE). ATXN1 encodes the polyglutamine protein ataxin-1, which works in the cell nucleus as a corepressor of gene transcription. However, considering the ubiquitous expression of the ataxin-1 protein and the limitations of global Atxn1-null mouse models, the exact contribution of ataxin-1 to B-cell functioning and the overall EAE phenotype is not completely understood. To fill this gap, here we employed CRISPR-mediated genomic editing to develop the first conditional-knockout mouse line lacking ataxin-1 in the B-cell compartment. Using this novel in vivo model, we demonstrated that ataxin-1 regulates B-cell proliferation and activation in a cell-autonomous fashion, and decreases the activation of T cells and monocytes through indirect mechanisms. We also found that depleting ataxin-1 in B cells affects cytokine and immunoglobulin release in response to encephalitogenic challenges, but it is insufficient to modify the trajectory and neuropathology of the EAE model. Altogether, these results pinpoint a complex regulatory role for ataxin-1 in autoimmune demyelination involving multiple cellular targets.","journal":"FEBS Journal","year":2025,"id":535368,"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":0.9607,"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":1419466,"name":"Rachael Riley Denbrock","orcid":null,"position":1,"is_corresponding":false},{"id":1419467,"name":"Cindy Carolina Martines","orcid":null,"position":2,"is_corresponding":false},{"id":331931,"name":"Alessandro Didonna","orcid":"0000-0001-7510-9658","position":3,"is_corresponding":false},{"id":730506,"name":"Jonathan J. Carver","orcid":null,"position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41224709","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":[]}