| First Author | Couldrey C | Year | 2005 |
| Journal | Blood | Volume | 105 |
| Issue | 4 | Pages | 1476-83 |
| PubMed ID | 15498858 | Mgi Jnum | J:96602 |
| Mgi Id | MGI:3531030 | Doi | 10.1182/blood-2004-06-2302 |
| Citation | Couldrey C, et al. (2005) A STAT5 modifier locus on murine chromosome 7 modulates engraftment of hematopoietic stem cells during steady-state hematopoiesis. Blood 105(4):1476-83 |
| abstractText | Homologous disruption of expression of signal transducer and activator of transcription 5a (STAT5a) and STAT5b (STAT5ab(-/-)) in mice results in hematopoietic stem cells (HSCs) that can engraft irradiated hosts alone but are noncompetitive against wild-type HSCs. To explore mechanisms for this phenotype, we crossed the STAT5 mutations onto an HW80 background congenic to the original C57BL/6 that differs in a small chromosome 7 genomic locus. We previously demonstrated that C57BL/6 or HW80 background STAT5ab(-/-) bone marrow (BM) cells showed equal repopulating function either competitively or noncompetitively in irradiated hosts. However, one intraperitoneal injection of wild-type green fluorescent protein (GFP) transgenic BM cells into unconditioned newborn STAT5ab(-/-) recipients of either background was sufficient for high-level donor engraftment. Furthermore, haploinsufficiency of STAT5 (STAT5ab(+/-)) allowed improved engraftment over wild-type recipients, indicating a dose-dependent requirement for STAT5 activation. In reciprocal experiments, STAT5ab(-/-) BM was transplanted into nonirradiated W/W(v) hosts. In these mice, C57BL/6 STAT5ab(-/-) BM cells were 10-fold more defective in long-term engraftment than control wild-type BM cells and HW80 STAT5ab(-/-) BM cells were 5- to 10-fold more defective than C57BL/6 STAT5ab(-/-) BM cells. Therefore, we conclude that STAT5 plays a critical role during steady-state HSC engraftment and a chromosome 7 modifier locus regulates this activity. |
