A humanized mouse model for a common beta0-thalassemia mutation.

Abstract

Accurate animal models that recapitulate the phenotype and genotype of patients with beta-thalassemia would enable the development of a range of possible therapeutic approaches. Here we report the generation of a mouse model carrying the codons 41-42 (-TTCT) beta-thalassemia mutation in the intact human beta-globin locus. This mutation accounts for approximately 40% of beta-thalassemia mutations in southern China and Thailand. We demonstrate a low level of production of gamma-globins from the mutant locus in day 18 embryos, as well as production of mutant human beta-globin mRNA. However, in contrast to transgenic mice carrying the normal human beta-globin locus, 4-bp deletion mice fail to show any phenotypic complementation of the knockout mutation of both murine beta-globin genes. Our studies suggest that this is a valuable model for gene correction in hemopoietic stem cells and for studying the effects of HbF inducers in vivo in a "humanized" thalassemic environment.

• Authors: Duangporn Jamsai, Faten Zaibak, Wantana Khongnium, Jim Vadolas, Lucille Voullaire, Kerry J Fowler, Sophie Gazeas, Suthat Fucharoen, Robert Williamson, Panayiotis A Ioannou
• Journal: Genomics (Genomics) Vol. 85 Issue 4 Pg. 453-61 (Apr 2005) ISSN: 0888-7543 [Print] United States
• PMID: 15780748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Globins

Topics

• Animals
• Disease Models, Animal
• Embryo, Mammalian (abnormalities)
• Erythrocytes, Abnormal (cytology)
• Gene Expression
• Globins (analysis, genetics, metabolism)
• Humans
• Mice (genetics)
• Mice, Knockout
• Phenotype
• Sequence Deletion
• Transgenes
• beta-Thalassemia (genetics)