A mouse model for beta-thalassemia.
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A mutation that produces an absolute deficiency of normal beta-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 beta-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 beta-major globin. Based on genetic and hematological criteria, mice homozygous for the mutant allele, designated Hbbth-1, represent the first animal model of beta-thalassemia (Cooley's anemia), a severe genetic disease of humans.
author list (cited authors)
Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Popp, D. M., Goldberg, S. Z., ... Lewis, S. E.
complete list of authors
Skow, LC||Burkhart, BA||Johnson, FM||Popp, RA||Popp, DM||Goldberg, SZ||Anderson, WF||Barnett, LB||Lewis, SE