A mouse model for β-thalassemia |
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Authors: | LC Skow BA Burkhart FM Johnson RA Popp DM Popp SZ Goldberg WF Anderson LB Barnett SE Lewis |
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Institution: | 1. Laboratory of Genetics National Institute of Environmental Health Sciences Research Triangle Park, North Carolina 27709 USA;2. Biology Division Oak Ridge National Laboratory Oak Ridge, Tennessee 37830 USA;3. Laboratory of Molecular Hematology National Heart, Lung, and Blood Institute Bethesda, Maryland 20205 USA;4. Chemistry and Life Sciences Group Research Triangle Institute Research Triangle Park, North Carolina 27709 USA |
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Abstract: | A mutation that produces an absolute deficiency of normal β-major globin polypeptides has been recovered from a DBA/2J male mouse. Most mice homozygous for the deficiency survived to adulthood and reproduced but were smaller at birth than their littermates and demonstrated a hypochromic, microcytic anemia with severe anisocytosis, poikilocytosis, and reticulocytosis and the presence of inclusion bodies in a high proportion of circulating erythrocytes. Mice heterozygous for the deficiency demonstrated a mild reticulocytosis but were not clinically anemic. Analysis of globin chain synthesis in vitro by 3H-leucine incorporation revealed that β-globin synthesis was nearly normal (95%) in heterozygotes and about 75% of normal in deficiency homozygotes. Molecular characterization of the mutation by restriction analysis revealed a deletion of about 3.3 kb of DNA, including regulatory sequences and all coding blocks for β-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele, designated Hbbth-1, represent the first animal model of β-thalassemia (Cooley's anemia), a severe genetic disease of humans. |
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