Mouse model of human β0 thalassemia: Targeted deletion of the mouse β(maj)- and β(min)-globin genes in embryonic stem cells

Academic Article

Abstract

  • β0-Thalassemia is an inherited disorder characterized by the absence of β-globin polypeptides derived from the affected allele. The molecular basis for this deficiency is a mutation of the adult β-globin structural gene or cis regulatory elements that control β-globin gene expression. A mouse model of this disease would enable the testing of therapeutic regimens designed to correct the defect. Here we report a 16-kb deletion that includes both adult β-like globin genes, β(maj) and β(min), in mouse embryonic stem cells. Heterozygous animals derived from the targeted cells are severely anemic with dramatically reduced hemoglobin levels, abnormal red cell morphology, splenomegaly, and markedly increased reticulocyte counts. Homozygous animals die in utero; however, heterozygous mice are fertile and transmit the deleted allele to progeny. The anemic phenotype is completely rescued in progeny derived from mating β0-thalassemic animals with transgenic mice expressing high levels of human hemoglobin A. The β0-thalassemic mice can be used to test genetic therapies for β0-thalassemia and can be bred with transgenic mice expressing high levels of human hemoglobin HbS to produce an improved mouse model of sickle cell disease.
  • Digital Object Identifier (doi)

    Author List

  • Ciavatta DJ; Ryan TM; Farmer SC; Townes TM
  • Start Page

  • 9259
  • End Page

  • 9263
  • Volume

  • 92
  • Issue

  • 20