| First Author | Scott LM | Year | 2003 |
| Journal | Mol Cell Biol | Volume | 23 |
| Issue | 24 | Pages | 9349-60 |
| PubMed ID | 14645544 | Mgi Jnum | J:86861 |
| Mgi Id | MGI:2682178 | Doi | 10.1128/MCB.23.24.9349-9360.2003 |
| Citation | Scott LM, et al. (2003) Deletion of alpha4 integrins from adult hematopoietic cells reveals roles in homeostasis, regeneration, and homing. Mol Cell Biol 23(24):9349-60 |
| abstractText | We have explored the functional implications of inducible alpha4 integrin deletion during adult hematopoiesis by generating a conditional-knockout mouse model, and we show that alpha4 integrin-deficient hematopoietic progenitor cells accumulate in the peripheral blood soon after interferon-induced gene deletion. Although their numbers gradually stabilize at a lower level, progenitor cell influx into the circulation continues at above-normal levels for more than 50 weeks. Concomitantly, a progressive accumulation of progenitors occurs within the spleen. In addition, the regeneration of erythroid and myeloid progenitor cells is delayed during stress hematopoiesis induced by phenylhydrazine or by 5-fluorouracil, suggesting impairment in early progenitor expansion in the absence of alpha4 integrin. Moreover, in transplantation studies, homing of alpha4(-/-) cells to the bone marrow, but not to the spleen, is selectively impaired, and short-term engraftment is critically delayed in the early weeks after transplantation. Thus, conditional deletion of alpha4 integrin in adult mice is accompanied by a novel hematopoietic phenotype during both homeostasis and recovery from stress, a phenotype that is distinct from the ones previously described in alpha4 integrin-null chimeras and beta1 integrin-conditional knockouts. |
