Inactivation of mouse alpha-globin gene by homologous recombination: mouse model of hemoglobin H disease.
نویسندگان
چکیده
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.
منابع مشابه
Inactivation of Mouse & - Globin Gene by Homologous Recombination : Mouse Model of Hemoglobin H Disease
HE HUMAN a-globin locus is located on chromosome 16 and is arranged in the order of ($(aa.’ The common molecular mechanism giving rise to a-thalassemia is caused by deletion of the a-globin structural genes. Because the a-globin genes are duplicated, a-thalassemia could result in three phenotypes. When one of the four a-globin genes in the diploid genome is deleted (-a/aa), a clinically silent ...
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ورودعنوان ژورنال:
- Blood
دوره 88 5 شماره
صفحات -
تاریخ انتشار 1996