{"doi":"10.1101/2021.01.29.428877","title":"Dysregulation of PAX5 causes uncommitted B cell development and tumorigenesis in mice","abstract":"Abstract PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in PAX5 account for 30% of B cell acute lymphoblastic leukemia (B-ALL) cases. Investigating the causal effects of PAX5 mutations has however been difficult due to the premature lethality of Pax5 −/− mice. Here we describe a novel mouse strain with a premature STOP mutation in Pax5 (Y351*) that produces a truncated protein and reduction in protein function, yet still allows for some B cell development to occur. A population of uncommitted and multipotent CD19 + B220 − B cells develops in the bone marrow of homozygous mice leading to the development of B-ALL. We show that the tumors frequently acquire secondary mutations in Jak3 , and Ptpn11 highlighting key pathways interacting with PAX5 during malignant transformation. Analysis of the PAX5 Y351* mice provide insight not only into the functional consequence of reduced PAX5 activity on B cell development and identity, but also provides an avenue in which to study PAX5-driven B-ALL in mice. One Sentence Summary Reduction in PAX5 function in mice induces the development of uncommitted B cells that have multipotent and malignant potential.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217176,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"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":813640,"name":"Kaiyue Helian","orcid":"0000-0002-1833-1823","position":1,"is_corresponding":false},{"id":293170,"name":"T. 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Roots","orcid":null,"position":9,"is_corresponding":false},{"id":813645,"name":"Mehmet Yabas","orcid":"0000-0002-3462-5389","position":10,"is_corresponding":false},{"id":814009,"name":"Nadine Barthel","orcid":null,"position":11,"is_corresponding":false},{"id":813646,"name":"Sofia A. Omari","orcid":"0000-0003-0345-5601","position":12,"is_corresponding":false},{"id":813647,"name":"Clara Young","orcid":"0000-0002-9911-087X","position":13,"is_corresponding":false},{"id":656802,"name":"Lisa A. Miosge","orcid":"0000-0001-8317-3377","position":14,"is_corresponding":false},{"id":20055,"name":"Eduardo Eyras","orcid":"0000-0003-0793-6218","position":15,"is_corresponding":false},{"id":588727,"name":"Stephen L. Nutt","orcid":"0000-0002-0020-6637","position":16,"is_corresponding":false},{"id":813648,"name":"Nadine Hein","orcid":"0000-0002-9703-6899","position":17,"is_corresponding":false},{"id":249549,"name":"Katherine M. Hannan","orcid":"0000-0003-4186-8167","position":18,"is_corresponding":false},{"id":254842,"name":"Ian A. Cockburn","orcid":"0000-0001-8220-9294","position":19,"is_corresponding":false},{"id":656807,"name":"Christopher C. 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