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Originally published online as doi:10.1189/jlb.0206097 on August 3, 2006

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{alpha} in murine hematopoietic stem/progenitor cells

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

Departments of
* Cellular and Molecular Medicine and
{ddagger} Medicine, School of Medicine, and
{dagger} 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-{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 RXR{alpha} 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}, ß, and {gamma}) is limiting.

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




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