| First Author | Wang Q | Year | 2004 |
| Journal | Blood | Volume | 103 |
| Issue | 4 | Pages | 1278-85 |
| PubMed ID | 14576056 | Mgi Jnum | J:88223 |
| Mgi Id | MGI:3029784 | Doi | 10.1182/blood-2003-06-2158 |
| Citation | Wang Q, et al. (2004) BUBR1 deficiency results in abnormal megakaryopoiesis. Blood 103(4):1278-85 |
| abstractText | The physiologic function of BUBR1, a key component of the spindle checkpoint, was examined by generating BUBR1-mutant mice. BUBR1(-/-) embryos failed to survive beyond day 8.5 in utero as a result of extensive apoptosis. Whereas BUBR1(+/-) blastocysts grew relatively normally in vitro, BUBR1(-/-) blastocysts exhibited impaired proliferation and atrophied. Adult BUBR1(+/-) mice manifested splenomegaly and abnormal megakaryopoiesis. BUBR1 haploinsufficiency resulted in an increase in the number of splenic megakaryocytes, which was correlated with an increase in megakaryocytic, but a decrease in erythroid, progenitors in bone marrow cells. RNA interference-mediated down-regulation of BUBR1 also caused an increase in polyploidy formation in murine embryonic fibroblast cells and enhanced megakaryopoiesis in bone marrow progenitor cells. However, enhanced megakaryopoiesis in BUBR1(+/-) mice was not correlated with a significant increase in platelets in peripheral blood, which was at least partly due to a defect in the formation of proplatelet-producing megakaryocytes. Together, these results indicate that BUBR1 is essential for early embryonic development and normal hematopoiesis. |
