| First Author | Boast B | Year | 2021 |
| Journal | bioRxiv | Mgi Jnum | J:306017 |
| Mgi Id | MGI:6712635 | Doi | 10.1101/2021.01.29.428877 |
| Citation | Boast B, et al. (2021) Dysregulation of PAX5 causes uncommitted B cell development and tumorigenesis in mice. bioRxiv |
| abstractText | PAX5 is the master transcription factor controlling B cell identity. In humans, mutations in PAX5account for 30% of B cell acute lymphoblastic leukemia(B-ALL)cases. Investigating the causal effects of PAX5mutationshas 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 multipotentCD19+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,andPtpn11highlighting key pathways interacting with PAX5 during malignant transformation. Analysis of the PAX5Y351*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. |
