| First Author | Chari S | Year | 2010 |
| Journal | J Immunol | Volume | 185 |
| Issue | 1 | Pages | 410-7 |
| PubMed ID | 20511547 | Mgi Jnum | J:161438 |
| Mgi Id | MGI:4459330 | Doi | 10.4049/jimmunol.0903688 |
| Citation | Chari S, et al. (2010) Notch target gene deregulation and maintenance of the leukemogenic phenotype do not require RBP-Jkappa in Ikaros null mice. J Immunol 185(1):410-7 |
| abstractText | Ikaros and Notch are transcriptional regulators essential for normal T cell development. Aberrant activation of Notch target genes is observed in Ikaros-deficient thymocytes as well as leukemia cell lines. However, it is not known whether Notch deregulation plays a preferential or obligatory role in the leukemia that arise in Ikaros null (Ik(-/-)) mice. To answer this question, the expression of the DNA-binding Notch target gene activator RBP-Jkappa was abrogated in Ik(-/-) double-positive thymocytes. This was accomplished through conditional inactivation using CD4-Cre transgenic mice containing floxed RBP-Jkappa alleles (RBPJ(fl/fl)). Ik(-/-) x RBPJ(fl/fl) x CD4-Cre(+) transgenic mice develop clonal T cell populations in the thymus that escape to the periphery, with similar kinetics and penetrance as their CD4-Cre(-) counterparts. The clonal populations do not display increased RBP-Jkappa expression compared with nontransformed thymocytes, suggesting there is no selection for clones that have not fully deleted RBP-Jkappa. However, RBPJ-deficient clonal populations do not expand as aggressively as their RBPJ-sufficient counterparts, suggesting a qualitative role for deregulated Notch target gene activation in the leukemogenic process. Finally, these studies show that RBP-Jkappa plays no role in Notch target gene repression in double-positive thymocytes but rather that it is Ikaros that is required for the repression of these genes at this critical stage of T cell development. |
