Expression of the Globin Genes and Hematopoiesis in beta-Thalassemic Mice.

摘要

Normal mice have two beta-globin genes. Approximately 80 percent of the beta globin in adult mice is produced by the 5' beta-major globin gene and 20 percent by the 3' beta-minor globin gene. Homozygous beta-thalassemic mice do not produce any beta-dmajor globin because the entire beta-dmajor globin gene was removed by a spontaneous deletion of a 3.7 kb segment of DNA from mouse chromosome 7. The beta-dminor globin gene was left intact and adult beta-thalassemic mice produce only the beta-dminor globin. Analysis of gene products in mice with several combinations of hemoglobin gene mutations show that the amount of beta globin synthesized in homozygous beta-thalassemic mice is less than in normal mice; however, it is more than would be expected if expression of the beta- dminor globin gene remained at the same level in beta-thalassemic mice as in normal mice. While the amount of beta globin synthesized in beta-thalassemic mice is reduced, a normal quantity of alpha globin is synthesized. After all the beta globin is used to form alpha sub 2 beta sub 2 tetramers, the excess-alpha globin precipitates. The precipitate damages the erythrocyte membrane, and red cell survival is shortened. To maintain hemostasis, erythropoiesis is expanded. Data on the altered expression of the globin genes and on the perturbed hematopoiesis in beta-thalassemic mice are presented in this report. 38 refs., 4 figs., 6 tabs. (ERA citation 14:029434)