title: A mouse model for beta-thalassemia.
abstract: 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.
mesh_terms: D000818:Animals; D002872:Chromosome Deletion; D004247:DNA / Q000032:analysis; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013789:Thalassemia / Q000235:genetics*
chemical_list: D006454:Hemoglobins; D005914:Globins; D004247:DNA; D004262:DNA Restriction Enzymes