A humanized mouse model for a common β0-thalassemia mutation

Duangporn Jamsai, Faten Zaibak, Wantana Khongnium, Jim Vadolas, Lucille Voullaire, Kerry J Fowler, Sophie Gazeas, Suthat Fucharoen, Robert Williamson, Panayiotis A Ioannou

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47 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)453 - 461
Number of pages9
Issue number4
Publication statusPublished - 2005
Externally publishedYes

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