Ley T J, Maloney K A, Gordon J I, Schwartz A L
Department of Medicine, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri.
J Clin Invest. 1989 Mar;83(3):1032-8. doi: 10.1172/JCI113944.
We measured steady-state levels of the human globin mRNAs in liver samples from several mid-gestational fetuses. RNA from the epsilon, gamma, beta, zeta, theta, and alpha globin genes were present in fetal liver samples isolated from 10-25-wk embryos. The abundance of all human globin mRNAs declined in older fetuses, presumably because of a gradual reduction in the proportion of erythroid precursors in the liver as development proceeds. The gamma:beta globin mRNA ratio in 10-18-wk fetal erythroblasts was 6-7:1, and in adult erythroid bone marrow the ratio was 0.02:1. In fetal liver samples, the relative abundance of epsilon transcripts was less than 1% that of gamma, and zeta transcripts less than 5% that of alpha. Embryonic transcripts declined in abundance during late fetal development and were not detected in newborn liver or adult erythroid bone marrow. theta globin mRNA also represented a minor species (less than 1% that of alpha) in fetal liver samples, but in contrast to the embryonic mRNAs, was most abundant in adult marrow samples obtained from patients with erythroid hyperplasia. These results support the hypothesis that globin protein levels are regulated by the relative amounts of each globin mRNA at various stages of erythropoietic development.
我们检测了来自几个中期妊娠胎儿肝脏样本中人类珠蛋白mRNA的稳态水平。从10至25周胚胎分离出的胎儿肝脏样本中存在来自ε、γ、β、ζ、θ和α珠蛋白基因的RNA。在较大的胎儿中,所有人类珠蛋白mRNA的丰度均下降,推测是因为随着发育的进行,肝脏中红细胞前体的比例逐渐降低。10至18周胎儿成红细胞中γ:β珠蛋白mRNA的比例为6 - 7:1,而在成人红细胞骨髓中该比例为0.02:1。在胎儿肝脏样本中,ε转录本的相对丰度不到γ的1%,ζ转录本不到α的5%。胚胎转录本在胎儿发育后期丰度下降,在新生儿肝脏或成人红细胞骨髓中未检测到。θ珠蛋白mRNA在胎儿肝脏样本中也占少数(不到α的1%),但与胚胎mRNA不同的是,在从红细胞增生患者获得的成人骨髓样本中最为丰富。这些结果支持了这样一种假说,即珠蛋白水平在红细胞生成发育的各个阶段受每种珠蛋白mRNA相对量的调节。