title: Mutation in murine erythropoietin receptor induces erythropoietin-independent erythroid proliferation in vitro, polycythemia in vivo.
abstract: Erythropoietin (Epo) is the major regulator of erythroid viability, proliferation, and differentiation. These functions are transduced following binding of Epo to a specific cell surface receptor, the erythropoietin receptor (EpoR), a member of a new cytokine receptor superfamily of receptors. An activating mutation in the murine EpoR has been described (cEpoR) and confers growth factor-independent growth upon an IL-3-dependent pro-B cell. To determine the effect of an activating mutation in the EpoR upon erythropoiesis specifically and hematopoiesis generally, we infected hematopoietic progenitors and mice with a recombinant erythroleukemic spleen focus-forming virus (SFFV), lacking its pathogenic env gene but expressing cEpoR (SFFVcEpoR). In vitro, infection with SFFVcEpoR resulted in factor-independent growth and development of CFU-Es yet had no effect on BFU-E growth, mixed colony growth, or myeloid colony growth. Mice infected with SFFVcEpoR, but not a virus expressing wild type EpoR (SFFVEpoR), developed erythrocytosis and splenomegaly.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
authors.forename: G D
authors.initials: GD
authors.lastname: Longmore
authors.forename: P
authors.initials: P
authors.lastname: Pharr
authors.forename: H F
authors.initials: HF
authors.lastname: Lodish
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004912:Erythrocytes / Q000166:cytology*; D015672:Erythroid Precursor Cells; D004921:Erythropoietin / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000235:genetics*; D011087:Polycythemia Vera / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics*; D017467:Receptors, Erythropoietin; D013163:Splenomegaly / Q000209:etiology
chemical_list: D011956:Receptors, Cell Surface; D017467:Receptors, Erythropoietin; D004921:Erythropoietin