title: Lethal thalassemia after insertional disruption of the mouse major adult beta-globin gene.
abstract: Thalassemias are hereditary anemias caused by mutations that disturb the normal 1:1 balance of alpha- and beta-globin chains that form hemoglobin. We have disrupted the major adult beta-globin gene (b1) in mouse embryonic stem cells by using homologous recombination to insert selectable sequences into the gene. Mice homozygous for this insertional disruption of the b1 gene (Hbbth-2/Hbbth-2) are severely anemic and die perinatally. In contrast, approximately 60% of mice homozygous for deletion of the same gene (Hbbth-1/Hbbth-1) survive to adulthood and are much less anemic [Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Goldberg, S. Z., Anderson, W. F., Barnett, L. B. & Lewis, S. E. (1983) Cell 34, 1043-1052]. These different phenotypes have implications for the control of beta-globin gene expression.
authors: Department of Pathology, University of North Carolina, Chapel Hill 27599-7525.
authors: W R
authors: WR
authors: Shehee
authors: P
authors: P
authors: Oliver
authors: O
authors: O
authors: Smithies
mesh_terms: D000818:Animals; D001483:Base Sequence; D005804:Genes, Lethal; D005914:Globins / Q000235:genetics*; D006400:Hematocrit; D006441:Hemoglobin A / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009838:Oligodeoxyribonucleotides; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D011995:Recombination, Genetic; D015183:Restriction Mapping; D013789:Thalassemia / Q000097:blood / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D005914:Globins; D006441:Hemoglobin A