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Publication : Normal hematopoiesis after conditional targeting of RXRalpha in murine hematopoietic stem/progenitor cells.

First Author  Ricote M Year  2006
Journal  J Leukoc Biol Volume  80
Issue  4 Pages  850-61
PubMed ID  16888087 Mgi Jnum  J:113089
Mgi Id  MGI:3664490 Doi  10.1189/jlb.0206097
Citation  Ricote M, et al. (2006) Normal hematopoiesis after conditional targeting of RXRalpha in murine hematopoietic stem/progenitor cells. J Leukoc Biol 80(4):850-61
abstractText  Because of the retinoic acid receptor-alpha (RARalpha) gene's involvement in acute promyelocytic leukemia, the important role of RARs in hematopoiesis is now well established. However, relatively few studies of hematopoiesis have focused on the role of the retinoid X receptors (RXRs), the obligate heterodimeric partners of the RARs. We sought to establish whether conditional targeting of RXRalpha in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic targeting of RXRalpha, we characterized IFN-inducible MxCre mice for use in studying the role of RXRalpha in hematopoiesis. We established that MxCre executes recombination of loxP-flanked RXRalpha in hematopoietic progenitors immunophenotypically enriched for HSC, leading to widespread and sustained targeting of RXRalpha in hematopoietic cells. However, we found no evidence of hematologic compromise in mice lacking RXRalpha, suggesting that RXRalpha is dispensable for normal murine hematopoiesis. Nonetheless, RXRalpha null bone marrow cells cultured in methylcellulose form colonies more efficiently than bone marrow cells obtained from control mice. This result suggests that although RXRalpha is not required for murine hematopoiesis, there may be hematopoietic signaling pathways that respond selectively to RXRalpha or settings in which combined expression of RXR (alpha, beta, and gamma) is limiting.
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