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Published online before print August 3, 2006

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(Journal of Leukocyte Biology. 2006;80:850-861.)
© 2006 by Society for Leukocyte Biology

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

Mercedes Ricote^*,1,2, Cynthia S. Snyder^*,1, Ho-Yin Leung^*, Ju Chen, Kenneth R. Chien^,3 and Christopher K. Glass^*,

Departments of
^* Cellular and Molecular Medicine and
Medicine, School of Medicine, and
Institute of Molecular Medicine, University of California, La Jolla, San Diego

² Correspondence and current address: Centro Nacional de Investigaciones Cardiovasculares (CNIC), Melchor Fernández Almagro, 3, Madrid 28029, Spain. E-mail: mricote{at}cnic.es

Because of the retinoic acid receptor- (RAR) 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 in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic targeting of RXR, we characterized IFN-inducible 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 sustained 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 hematopoiesis. Nonetheless, RXR 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 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 (, ß, and ) is limiting.

Key Words: myelopoiesis • nuclear receptors • retinoid X receptors • retinoic acid receptors