Normal hematopoiesis after conditional targeting of RXRα in murine hematopoietic stem/progenitor cells

Because of the retinoic acid receptor- (RAR) gene's involvement in acute promyelocytic leukemia, the important role of RARs in hemato- poiesis is now well established. However, relatively few studies of hematopoiesis have focused on the role of the retinoid X receptors (RXRs), the obli- gate heterodimeric partners of the RARs. We sought to establish whether conditional targeting of RXR in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoi- etic targeting of RXR, we characterized IFN-in- ducible MxCre mice for use in studying the role of RXR in hematopoiesis. We established that MxCre executes recombination of loxP-flanked RXR in hematopoietic progenitors immunophenotypically enriched for HSC, leading to widespread and sus- tained targeting of RXR in hematopoietic cells. However, we found no evidence of hematologic compromise in mice lacking RXR, suggesting that RXR is dispensable for normal murine hemato- poiesis. Nonetheless, RXR null bone marrow cells cultured in methylcellulose form colonies more ef- ficiently than bone marrow cells obtained from control mice. This result suggests that although RXR is not required for murine hematopoiesis, there may be hematopoietic signaling pathways that respond selectively to RXR or settings in which combined expression of RXR (, , and )i s limiting. J. Leukoc. Biol. 80: 850-861; 2006.