First Author | Jamsai D | Year | 2005 |
Journal | Genomics | Volume | 85 |
Issue | 4 | Pages | 453-61 |
PubMed ID | 15780748 | Mgi Jnum | J:97548 |
Mgi Id | MGI:3575624 | Doi | 10.1016/j.ygeno.2004.11.016 |
Citation | Jamsai D, et al. (2005) A humanized mouse model for a common beta0-thalassemia mutation. Genomics 85(4):453-61 |
abstractText | 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. |