| First Author | Sandberg ML | Year | 2005 |
| Journal | Dev Cell | Volume | 8 |
| Issue | 2 | Pages | 153-66 |
| PubMed ID | 15691758 | Mgi Jnum | J:96507 |
| Mgi Id | MGI:3530730 | Doi | 10.1016/j.devcel.2004.12.015 |
| Citation | Sandberg ML, et al. (2005) c-Myb and p300 regulate hematopoietic stem cell proliferation and differentiation. Dev Cell 8(2):153-66 |
| abstractText | Precise control of hematopoietic stem cell (HSC) proliferation and differentiation is needed to maintain a lifetime supply of blood cells. Using genome-wide ENU mutagenesis and phenotypic screening, we have identified a mouse line that harbors a point mutation in the transactivation (TA) domain of the transcription factor c-Myb (M303V), which reduces c-Myb-dependent TA by disrupting its interaction with the transcriptional coactivator p300. The biological consequences of the c-Myb(M303V/M303V) mutation include thrombocytosis, megakaryocytosis, anemia, lymphopenia, and the absence of eosinophils. Detailed analysis of hematopoiesis in c-Myb(M303V/M303V) mice reveals distinct blocks in T cell, B cell, and red blood cell development, as well as a remarkable 10-fold increase in the number of HSCs. Cell cycle analyses show that twice as many HSCs from c-Myb(M303V/M303V) animals are actively cycling. Thus c-Myb, through interaction with p300, controls the proliferation and differentiation of hematopoietic stem and progenitor cells. |
