K-Ras is essential for normal fetal liver erythropoiesis.
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.
Khalaf
Waleed F
WF
Indiana University School of Medicine, Herman B Wells Center for Pediatric Research, 1044 W Walnut St R4/470, Indianapolis, IN 46202, USA.
White
Hilary
H
Wenning
Mary Jo
MJ
Orazi
Attilio
A
Kapur
Reuben
R
Ingram
David A
DA
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*
D020033:Protein Isoforms; D018631:ras Proteins