title: Functional p85alpha gene is required for normal murine fetal erythropoiesis.
abstract: In vitro studies suggest that activation of class IA phosphatidylinositol 3 (PI-3) kinase is necessary for normal erythroid cell development. However, when class IA PI-3 kinase-deficient mice were generated by a targeted deletion of the p85alpha regulatory subunit, fetal erythropoiesis was reportedly unaffected. Given the discrepancies between these studies, we performed a more detailed in vivo analysis of class IA PI-3 kinase-deficient embryos. Day-14.5 p85alpha-/- embryos are pale with a marked reduction of mature erythrocytes in their peripheral blood. Further, the absolute number and frequency of both early (erythroid burst-forming unit [BFU-E]) and late erythroid progenitors (erythroid colony-forming unit [CFU-E]) are reduced in p85alpha-/- fetal livers compared with wild-type controls, which is associated with reduced proliferation. Taken together, these data establish an important role for p85alpha and class IA PI-3 kinase in regulating the development of both early and late erythroid progenitors in fetal liver.
authors.affiliation: Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut St, R4/470, Indianapolis, IN 46202, USA.
authors.forename: Hannah
authors.initials: H
authors.lastname: Huddleston
authors.forename: Bailin
authors.initials: B
authors.lastname: Tan
authors.forename: Feng-Chun
authors.initials: FC
authors.lastname: Yang
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: Mervin C
authors.initials: MC
authors.lastname: Yoder
authors.forename: Reuben
authors.initials: R
authors.lastname: Kapur
authors.forename: David A
authors.initials: DA
authors.lastname: Ingram
mesh_terms: D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002455:Cell Division; D015672:Erythroid Precursor Cells / Q000166:cytology; D004920:Erythropoiesis / Q000235:genetics*; D005333:Fetus; D005796:Genes / Q000502:physiology*; D008099:Liver; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000502:physiology
chemical_list: D019869:Phosphatidylinositol 3-Kinases