Functional p85alpha gene is required for normal murine fetal erythropoiesis.
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.
Huddleston
Hannah
H
Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W Walnut St, R4/470, Indianapolis, IN 46202, USA.
Tan
Bailin
B
Yang
Feng-Chun
FC
White
Hilary
H
Wenning
Mary Jo
MJ
Orazi
Attilio
A
Yoder
Mervin C
MC
Kapur
Reuben
R
Ingram
David A
DA
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
D019869:Phosphatidylinositol 3-Kinases