Developmental expression of NADPH phagocytic oxidase components in mouse embryos

We wished to determine when each of the four NADPH oxidase components p22 p hagocytic oxidase (phox), gp91 phox, p47 phox, p67 phox is first expressed embryologically and whether the expression pattern occurs in a consistent t emporal sequence or whether the four genes are expressed simultaneously. A deficiency of any one of them results in chronic granulomatous disease (CGD ). mRNA transcripts and protein expression for p22 phox, gp91 phox, p47 pho x, p67 phox was monitored in murine embryos at time of implantation (E5.5) until E 11.5, and in fetal liver, spleen, and limb bone marrow from E 14 un til term (E 19). We observed that mRNA was first expressed for p22 phox at E 5.5, for p67 phox at E 7.0 and for p47 phox at E 7.5 before the onset of yolk sac hematopoiesis (E 8.0). gp91 Phox mRNA was first expressed at E 9.0 . However, only p22 phox protein was expressed in circulating hemocytoblast by E 9.0. No other embryonic tissue contained phox proteins either before or after the establishment of hemocytoblastic circulation. The four specifi c mRNA transcripts and phox proteins were expressed in nests of developing granulocytes in liver by E 14 and the expression continued in the liver at E 16 and E 19. Spleen and limb bone marrow showed inconsistent results. Cor d blood neutrophils contained all phox proteins: These studies confirm that the four CGD-related phox mRNA components of NADPH oxidase are expressed e arly in embryonic development and the expression occurs in a consistent seq uential fashion but only p22 phox protein appears in embryonic hemocytoblas t.