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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3244-3252. Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-09-046672. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-09-046672v1 109/8/3244    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Heikens, M. J. Articles by Tsai, S. Search for Related Content PubMed PubMed Citation Articles by Heikens, M. J. Articles by Tsai, S. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Penumbra encodes a novel tetraspanin that is highly expressed in erythroid progenitors and promotes effective erythropoiesis Marc J. Heikens1, Thai M. Cao1, Chikako Morita1, Sarah L. DeHart1, and Schickwann Tsai1 1 Division of Hematology, Department of Medicine, University of Utah, Salt Lake City In a search for new genes involved in the regulation of erythropoiesis, we identified murine Penumbra cDNA from a multipotent hematopoietic cell line based on its predominant expression in erythroblasts. Subsequently, we identified the human PENUMBRA from a bone marrow cDNA library. Penumbra is a new member of the tetraspanin superfamily of membrane proteins, many of which are thought to function as organizers of supramolecular signaling complexes. Human and murine Penumbras contain 283 amino acids and are 97% identical. The human PENUMBRA gene is mapped to chromosome 7q32, a hot spot for deletions in myelodysplastic syndromes and acute myelogenous leukemias. Penumbra is targeted to the cell surface and forms disulfide-bonded homodimers. To study the effects of Penumbra deletions, we created a knockout mouse model by gene targeting. Penumbra–/– mice develop massive splenomegaly, basophilic macrocytic red blood cells, and anemia as they age. A multipotent hematopoietic cell line, EMX, was established from the bone marrow of a Penumbra–/– mouse. EMX exhibits ineffective erythropoiesis in the presence of erythropoietin, a defect that is reversed by reexpression of Penumbra. These findings indicate that Penumbra has a positive function in erythropoiesis and its deletion or mutation may result in anemia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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