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Although <jats:italic>Abin1<\/jats:italic> is located on chromosome 5q in the region commonly deleted in patients with 5q minus syndrome, the most distinct of the myelodysplastic syndromes (MDSs), the precise role of ABIN1 in MDSs remains unknown. In this study, mice with a mutation disrupting the polyubiquitin\u2010binding site (<jats:italic>Abin1<jats:sup>Q478H\/Q478H<\/jats:sup><\/jats:italic>) is generated. These mice develop MDS\u2010like diseases characterized by anemia, thrombocytopenia, and megakaryocyte dysplasia. Extramedullary hematopoiesis and bone marrow failure are also observed in <jats:italic>Abin1<jats:sup>Q478H\/Q478H<\/jats:sup><\/jats:italic> mice. Although <jats:italic>Abin1<jats:sup>Q478H\/Q478H<\/jats:sup><\/jats:italic> cells are sensitive to RIPK1 kinase\u2013RIPK3\u2013MLKL\u2010dependent necroptosis, only anemia and splenomegaly are alleviated by RIPK3 deficiency but not by MLKL deficiency or the RIPK1 kinase\u2010dead mutation. This indicates that the necroptosis\u2010independent function of RIPK3 is critical for anemia development in <jats:italic>Abin1<jats:sup>Q478H\/Q478H<\/jats:sup><\/jats:italic> mice. Notably, Abin1<jats:sup>Q478H\/Q478H<\/jats:sup> mice exhibit higher levels of type I interferon (IFN\u2010I) expression in bone marrow cells compared towild\u2010type mice. Consistently, blocking type I IFN signaling through the co\u2010deletion of <jats:italic>Ifnar1<\/jats:italic> greatly ameliorated anemia, thrombocytopenia, and splenomegaly in <jats:italic>Abin1<jats:sup>Q478H\/Q478H<\/jats:sup><\/jats:italic> mice. Together, these results demonstrates that ABIN1(Q478) prevents the development of hematopoietic deficiencies by regulating type I IFN expression.<\/jats:p>","DOI":"10.1002\/advs.202303555","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T19:09:46Z","timestamp":1701112186000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ABIN1 (Q478) is Required to Prevent Hematopoietic Deficiencies through Regulating Type I IFNs Expression"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4623-1907","authenticated-orcid":false,"given":"Xuanhui","family":"Wu","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety Shanghai Institute of Nutrition and Health University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 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