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

Because of the retinoic acid receptor-alpha (RAR alpha) 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 RXR alpha in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic targeting of RXR alpha, we characterized IFN-inducible MxCre mice for use in studying the role of RXR alpha in hematopoiesis. We established that MxCre executes recombination of loxP-flanked RXRa in hematopoietic progenitors immunophenotypically enriched for HSC, leading to widespread and sustained targeting of RXR alpha in hematopoietic cells. However, we found no evidence of hematologic compromise in mice lacking RXR alpha, suggesting that RXR alpha is dispensable for normal murine hematopoiesis. Nonetheless, RXR alpha null bone marrow cells cultured in methylcellulose form colonies more efficiently than bone marrow cells obtained from control mice. This result suggests that although RXR alpha is not required for murine hematopoiesis, there may be hematopoietic signaling pathways that respond selectively to RXR alpha or settings in which combined expression of RXR (alpha, beta, and gamma) is limiting.