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Prepublished online as a Blood First Edition Paper on May 31, 2002; DOI 10.1182/blood-2002-01-0124. This Article Full Text (PDF) All Versions of this Article: 2002-01-0124v1 100/7/2279    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Suzuki, N. Articles by Yamamoto, M. Search for Related Content PubMed PubMed Citation Articles by Suzuki, N. Articles by Yamamoto, M. Social Bookmarking                   What's this? Submitted January 16, 2002 Accepted March 15, 2002 Erythroid-specific expression of the erythropoietin receptor rescued its null mutant mice from lethality Norio Suzuki, Osamu Ohneda, Satoru Takahashi, Masato Higuchi, Harumi Y Mukai, Tatsutoshi Nakahata, Shigehiko Imagawa, and Masayuki Yamamoto* Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan Product Research Laboratory, Chugai Pharmaceutical Co Ltd, Tokyo, Japan Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan Center for Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan; Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan * Corresponding author; email: masi{at}tara.tsukuba.ac.jp. Erythropoietin (Epo) and its receptor (EpoR) are indispensable to erythropoiesis. While additional roles such as neuroprotection and heart development have been reported for the Epo-EpoR system besides angiogenesis, the precise contribution of Epo-EpoR to these nonhematopoietic tissues requires clarification. Exploiting a GATA-1 minigene cassette with hematopoietic regulatory domains, we established two lines of transgene-rescued EpoR-null mutant mice expressing EpoR exclusively in the hematopoietic lineage. Surprisingly, despite the lack of EpoR expression in nonhematopoietic tissues, these mice develop normally and are fertile. As such, we could exploit them for analyzing the roles of the Epo-EpoR system in adult hematopoiesis and in nonhematopoietic tissues. These rescued lines showed a differential level of EpoR expression in erythroid cells; one expressed approximately 40%, while the other expressed 120% of the wild type EpoR level. A colony formation assay showed that erythroid progenitors in the two mutant lines exhibit distinct sensitivity to Epo. The circulating Epo level was much higher in the transgenic line with a lower EpoR expression. In response to induced anemia, the plasma Epo concentrations increased in both lines. Notably, the timing of the peak of plasma Epo concentration was delayed in both lines of rescued mice in comparison with wild type, suggesting that, in wild type mice, nonhematopoietic EpoR contributes to the regulation of plasma Epo concentration. We, thus, conclude that nonhematopoietic expression of EpoR is dispensable to normal mouse development and that the expression level of EpoR regulates erythropoiesis by controlling the sensitivity of erythroid progenitors to Epo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Sulahian, O. Cleaver, and L. J.-s. 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