Submitted September 11, 2006
Accepted November 30, 2006
Penumbra encodes a novel tetraspanin that is highly expressed in erythroid progenitors and promotes effective erythropoiesis
Marc J. Heikens, Thai M Cao, Chikako Morita, Sarah L DeHart, and Schickwann Tsai*
Division of Hematology, Dept of Medicine, University of Utah, Salt Lake City, UT
* Corresponding author; email: schickwann.tsai{at}hsc.utah.edu.
In a search for new genes that might be 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 hotspot for deletions in myelodysplatic 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 re-expression of Penumbra. These findings indicate that Penumbra has a positive function in erythropoiesis and its deletion or mutation may result in anemia.
