title: K-Ras is essential for normal fetal liver erythropoiesis.
abstract: In vitro studies suggest that Ras activation is necessary for erythroid cell development. However, genetic inactivation of the Ras isoforms H-Ras, N-Ras, and K-Ras in mice reportedly did not affect adult or fetal erythropoiesis, though K-Ras(-/-) embryos were anemic. Given these discrepancies, we performed a more detailed analysis of fetal erythropoiesis in K-Ras(-/-) embryos. Day-13.5 K-Ras(-/-) embryos were pale with a marked reduction of mature erythrocytes in their fetal livers. The frequency and number of both early (erythroid burst-forming unit [BFU-E]) and late erythroid progenitors (erythroid colony-forming unit [CFU-E]) were reduced in K-Ras(-/-) fetal livers compared with wild-type controls and displayed a delay in terminal erythroid cell maturation. Further, K-Ras(-/-) hematopoietic progenitors had reduced proliferation in response to erythropoietin and Kit ligand compared with control cells. Thus, these studies identify K-Ras as a unique Ras isoform that is essential for regulating fetal erythropoiesis in vivo.
authors.affiliation: Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, 1044 W Walnut St R4/470, Indianapolis, IN 46202, USA.
authors.forename: Waleed F
authors.initials: WF
authors.lastname: Khalaf
authors.forename: Hilary
authors.initials: H
authors.lastname: White
authors.forename: Mary Jo
authors.initials: MJ
authors.lastname: Wenning
authors.forename: Attilio
authors.initials: A
authors.lastname: Orazi
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
authors.forename: David A
authors.initials: DA
authors.lastname: Ingram
mesh_terms: D000740:Anemia / Q000209:etiology; D000818:Animals; D049109:Cell Proliferation; D004912:Erythrocytes / Q000166:cytology; D004920:Erythropoiesis; D005333:Fetus / Q000166:cytology; D006412:Hematopoietic Stem Cells; D008099:Liver / Q000196:embryology* / Q000201:enzymology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D020033:Protein Isoforms; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D020033:Protein Isoforms; D018631:ras Proteins