PMID- 16888087 OWN - NLM STAT- MEDLINE DCOM- 20070928 LR - 20071203 IS - 0741-5400 (Print) IS - 0741-5400 (Linking) VI - 80 IP - 4 DP - 2006 Oct TI - Normal hematopoiesis after conditional targeting of RXRalpha in murine hematopoietic stem/progenitor cells. PG - 850-61 AB - Because of the retinoic acid receptor-alpha (RARalpha) 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 RXRalpha in early hematopoietic progenitors, ideally to the level of the hematopoietic stem cell (HSC), would compromise hematopoiesis. For hematopoietic targeting of RXRalpha, we characterized IFN-inducible MxCre mice for use in studying the role of RXRalpha in hematopoiesis. We established that MxCre executes recombination of loxP-flanked RXRalpha in hematopoietic progenitors immunophenotypically enriched for HSC, leading to widespread and sustained targeting of RXRalpha in hematopoietic cells. However, we found no evidence of hematologic compromise in mice lacking RXRalpha, suggesting that RXRalpha is dispensable for normal murine hematopoiesis. Nonetheless, RXRalpha null bone marrow cells cultured in methylcellulose form colonies more efficiently than bone marrow cells obtained from control mice. This result suggests that although RXRalpha is not required for murine hematopoiesis, there may be hematopoietic signaling pathways that respond selectively to RXRalpha or settings in which combined expression of RXR (alpha, beta, and gamma) is limiting. FAU - Ricote, Mercedes AU - Ricote M AD - Department of Cellular and Molecular Medicine, University of California, La Jolla, San Diego, USA. mricote@cnic.es FAU - Snyder, Cynthia S AU - Snyder CS FAU - Leung, Ho-Yin AU - Leung HY FAU - Chen, Ju AU - Chen J FAU - Chien, Kenneth R AU - Chien KR FAU - Glass, Christopher K AU - Glass CK LA - eng GR - 2 P30 A23100-18/PHS HHS/United States GR - CA52599/CA/NCI NIH HHS/United States GR - HL67034/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060803 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Retinoid X Receptor alpha) RN - 0 (Retinoid X Receptor beta) RN - 0 (Retinoid X Receptor gamma) RN - 63231-63-0 (RNA) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) SB - IM MH - Animals MH - Gene Expression Profiling MH - Hematopoiesis/*immunology MH - Hematopoietic Stem Cells/*immunology MH - Integrases/immunology MH - Mice MH - Mice, Transgenic MH - RNA/genetics MH - Retinoid X Receptor alpha/genetics/*immunology MH - Retinoid X Receptor beta/genetics/immunology MH - Retinoid X Receptor gamma/genetics/immunology MH - Reverse Transcriptase Polymerase Chain Reaction/methods MH - Signal Transduction/immunology EDAT- 2006/08/05 09:00 MHDA- 2007/09/29 09:00 CRDT- 2006/08/05 09:00 PHST- 2006/08/05 09:00 [pubmed] PHST- 2007/09/29 09:00 [medline] PHST- 2006/08/05 09:00 [entrez] AID - jlb.0206097 [pii] AID - 10.1189/jlb.0206097 [doi] PST - ppublish SO - J Leukoc Biol. 2006 Oct;80(4):850-61. doi: 10.1189/jlb.0206097. Epub 2006 Aug 3.