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The BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    mouse model, harbouring Y\u2010linked\n                    <jats:italic>Tlr7<\/jats:italic>\n                    duplication on a polygenic susceptibility background, has been instrumental in elucidating the TLR7\u2013type I interferon (IFN1) axis central to SLE. This review positions BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    as a comparative model system and advances a mechanism\u2010aligned framework that maps murine models to human SLE endotypes (e.g., IFN1\u2010high vs. IFN\u2010\u03b3\u2010dominant; germinal center\u2010 vs. extrafollicular\u2010biased B\u2010cell responses) and links those endotypes to targeted interventions. We highlight the fidelity of BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    to IFN1\u2010high patient biology, and its contributions of polygenic susceptibility in driving immune cell dysregulation, cytokine imbalance, and therapeutic responsiveness to BAFF and IFN1 blockade. Notably, this model also recapitulates pathogenic pDC activation, highlighting its relevance for emerging pDC\u2010targeted strategies. By contrasting BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    with other prominent lupus\u2010prone strains (e.g., MRL\/\n                    <jats:italic>lpr<\/jats:italic>\n                    , NZBWF1, NZM2410, B6.SLE1\/2\/3, BXD2, and Kika), we benchmark its predictive value for clinical heterogeneity and treatment response. We synthesise insights from BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    studies, including those that informed FDA\u2010approved biologics, and discuss implications for next\u2010generation precision therapies. Collectively, we advocate for BXSB.\n                    <jats:italic>Yaa<\/jats:italic>\n                    as an essential pre\u2010clinical platform among complementary models to accelerate mechanism\u2010based drug development and enable stratified translation in SLE research.\n                  <\/jats:p>","DOI":"10.1111\/imm.70117","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:52:53Z","timestamp":1770079973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>BXSB<\/scp>\n                    .\n                    <i>Yaa<\/i>\n                    : A Translational Model of Toll\u2010Like Receptor 7\u2010Type I Interferon\u2010Driven Systemic Lupus Erythematosus"],"prefix":"10.1111","author":[{"given":"Britney","family":"Sison","sequence":"first","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colleen M.","family":"Farley","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John J.","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santhanam","family":"Lakshminarayanan","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Connecticut School of Medicine  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derry C.","family":"Roopenian","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-7439","authenticated-orcid":false,"given":"Chih\u2010Hao","family":"Chang","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory  Bar Harbor Maine USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,2]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-021-03033-8","article-title":"Integrated Analysis of Competing Endogenous RNA Networks in Peripheral Blood Mononuclear Cells of Systemic Lupus Erythematosus","volume":"19","author":"Song W.","year":"2021","journal-title":"Journal of Translational Medicine"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-021-00900-w"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01898-7"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2017.05.006"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","DOI":"10.1186\/s13293-019-0274-2","article-title":"Sex Differences in Clinical Presentation of Systemic Lupus Erythematosus","volume":"10","author":"Ramirez Sepulveda J. 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