TY - JOUR
T1 - Increasing haemoglobin β-chain synthesis in foetal development is associated with a declining γ- to α-mRNA ratio
AU - Kazazian, Haig H.
AU - Silverstein, Arthur M.
AU - Snyder, Pamela G.
AU - Vanbeneden , Rebecca J.
PY - 1976
Y1 - 1976
N2 - DURING human foetal development, the predominant haemoglobin in erythrocytes switches twice (Fig. 1). First, ε chains of embryonic haemoglobins in erythroblasts of yolk sac origin are replaced by γ chains of foetal haemoglobin and traces of β chains of adult haemoglobin. This switch occurs very early in foetal development, coincident with the appearance of a new type of peripheral erythrocyte of hepatic origin. Second, at about 32 weeks of gestation, predominantly γ-chain production gives way to increased β-chain synthesis within a constant cell type1. This double haemoglobin switch also occurs in other animals, including sheep 2. Not only is very little known about the biological basis for the switch from γ- to β-chain production, but the basic changes in gene activity involved in the switching process are obscure. An understanding of the γ to β switch has clinical importance, for if one could block the switch and increase γ-chain production, sickle cell anaemia and β-thalassaemia could be treated effectively. We present here data concerning changes in globin gene activity, as assessed by globin mRNA levels, which are temporally related to the turning up of β-chain synthesis. These observations were originally made in erythroid cells of aborted human foetuses and were extended to cells from foetal sheep.
AB - DURING human foetal development, the predominant haemoglobin in erythrocytes switches twice (Fig. 1). First, ε chains of embryonic haemoglobins in erythroblasts of yolk sac origin are replaced by γ chains of foetal haemoglobin and traces of β chains of adult haemoglobin. This switch occurs very early in foetal development, coincident with the appearance of a new type of peripheral erythrocyte of hepatic origin. Second, at about 32 weeks of gestation, predominantly γ-chain production gives way to increased β-chain synthesis within a constant cell type1. This double haemoglobin switch also occurs in other animals, including sheep 2. Not only is very little known about the biological basis for the switch from γ- to β-chain production, but the basic changes in gene activity involved in the switching process are obscure. An understanding of the γ to β switch has clinical importance, for if one could block the switch and increase γ-chain production, sickle cell anaemia and β-thalassaemia could be treated effectively. We present here data concerning changes in globin gene activity, as assessed by globin mRNA levels, which are temporally related to the turning up of β-chain synthesis. These observations were originally made in erythroid cells of aborted human foetuses and were extended to cells from foetal sheep.
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U2 - 10.1038/260067a0
DO - 10.1038/260067a0
M3 - Article
C2 - 1264198
AN - SCOPUS:0017235598
SN - 0028-0836
VL - 260
SP - 67
EP - 70
JO - Nature
JF - Nature
IS - 5546
ER -