A humanized mouse model for a common beta0-thalassemia mutation |
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Authors: | Jamsai Duangporn Zaibak Faten Khongnium Wantana Vadolas Jim Voullaire Lucille Fowler Kerry J Gazeas Sophie Fucharoen Suthat Williamson Robert Ioannou Panayiotis A |
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Affiliation: | CAGT Research Group, The Murdoch Children's Research Institute, Department of Paediatrics, The University of Melbourne, Royal Children's Hospital, Flemington Road, Melbourne, VIC 3052, Australia. |
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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. |
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