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

M Ricote, CS Snyder, HY Leung, J Chen… - Journal of leukocyte …, 2006 - academic.oup.com
M Ricote, CS Snyder, HY Leung, J Chen, KR Chien, CK Glass
Journal of leukocyte biology, 2006academic.oup.com
Because of the retinoic acid receptor-α (RARα) 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 RXRα in early hematopoietic progenitors, ideally to the level of the
hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic …
Abstract
Because of the retinoic acid receptor-α (RARα) 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 RXRα in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic targeting of RXRα, we characterized IFN-inducible MxCre mice for use in studying the role of RXRα in hematopoiesis. We established that MxCre executes recombination of loxP-flanked RXRα in hematopoietic progenitors immunophenotypically enriched for HSC, leading to widespread and sustained targeting of RXRα in hematopoietic cells. However, we found no evidence of hematologic compromise in mice lacking RXRα, suggesting that RXRα is dispensable for normal murine hematopoiesis. Nonetheless, RXRα null bone marrow cells cultured in methylcellulose form colonies more efficiently than bone marrow cells obtained from control mice. This result suggests that although RXRα is not required for murine hematopoiesis, there may be hematopoietic signaling pathways that respond selectively to RXRα or settings in which combined expression of RXR (α, β, and γ) is limiting.
Oxford University Press