The globin switch at the level of mRNA in the developing mouse.

We have carried out a detailed analysis of the relative amounts of zeta, alpha, beta H1, epsilon y2 and adult beta globin mRNA in different tissues of the mouse embryo from Day 8.5 to Day 17.5 i.e. from the first signs of erythropoiesis until almost the end of gestation (birth is Day 19). Interestingly, we find that the zeta to alpha "switch" occurs 24 hours earlier in yolk sac than it does in fetal liver and that the ratio of zeta to alpha mRNA remains higher in the peripheral blood than in the yolk sac or the fetal liver during the latter half of gestation. In fact, zeta mRNA remains present in peripheral blood until Day 15.5. The switch at the mRNA level appears to mimic that found by others [Popp et al, 1987] at the protein level, at least for peripheral blood. This suggests that regulation is not occurring to any major extent at the translational level. The reiteration of the switch in fetal liver suggests that local environmental factors are involved. We find two switches within the beta cluster; beta H1 is expressed first, then epsilon y2 and lastly the two adult beta globins (beta major and beta minor). The switch from beta H1 to epsilon y2 occurs around Day 11.5 and the switch from epsilon y2 to the adult beta globins occurs around Day 15.5. This means that the pattern of expression of the beta-like globin genes in the mouse is more analogous to that found in the human than was previously thought.