Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease.
We have disrupted the 5' locus of the duplicated adult alpha-globin genes by gene targeting in the mouse embryonic stem cells and created mice with alpha-thalassemia syndromes. The heterozygous knockout mice (.alpha/alpha alpha) are asymptomatic like the silent carriers in humans whereas the homozygous knockout mice (.alpha/.alpha) show hemolytic anemia. Mice with three dysfunctional alpha-globin genes generated by breeding the 5' alpha-globin knockouts (.alpha/alpha alpha) and the deletion type alpha-thalassemia mice (../alpha alpha) produce severe hemoglobin H disease and they die in utero. These results indicate that the 5' alpha-globin gene is the predominant locus in mice, and suggest that it is even more dominant than its human homologue.
Chang
J
J
Department of Laboratory Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.
Lu
R H
RH
Xu
S M
SM
Meneses
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Chan
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Pedersen
R
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Kan
Y W
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D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000166:cytology; D005313:Fetal Death / Q000235:genetics; D018390:Gene Targeting; D005799:Genes, Dominant; D005838:Genotype; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice / Q000196:embryology / Q000235:genetics*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D005810:Multigene Family; D011995:Recombination, Genetic; D017384:Sequence Deletion; D013234:Stem Cells; D017085:alpha-Thalassemia / Q000196:embryology / Q000235:genetics*
D005914:Globins