Expression of human beta E-globin gene with erythroid enhancer in transgenic mice.
The human beta E-globin gene from HbE (beta 26 Glu-->Lys, G-->A) homozygote, a common hemoglobinopathy in China, was injected into the pronuclei of fertilized mouse eggs to prepare transgenic mice. A transgenic mouse bearing 16 copies of construct 5'.HS2 beta E has characteristics of typical transgenic mice. It has been verified that the presence of erythroid enhancer 5'HS2 is necessary for the high level expression of human beta E-globin gene in transgenic mice, indicating that the cis-element 5'HS2 is effective for abnormal beta-globin gene as well. Although the expression level of beta-globin gene was copy number-dependent as reported in previous studies, the average expression level per gene copy (12.1%) in transgenic mice bearing many copies of 5'HS2 beta E (16 copies) was significantly lower than that (79.7%) in transgenic mice bearing fewer copies of the gene (2 copies). The possible mechanisms for this decrease of expression are discussed. Novel hemoglobin tetramers which presumably consist of human beta E-globin chains and mouse endogenous alpha-globin chains have been assembled in transgenic mice.
Liu
Q H
QH
State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing.
Liu
D P
DP
Ding
Y Z
YZ
Wei
Q Z
QZ
Jia
P C
PC
Chen
S S
SS
Liang
Z Q
ZQ
D000818:Animals; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005796:Genes; D005914:Globins / Q000235:genetics*; D006446:Hemoglobin E / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D017354:Point Mutation; D016133:Polymerase Chain Reaction
D005914:Globins; D006446:Hemoglobin E