A humanized mouse model for a common beta0-thalassemia mutation.
Genomics
; 85(4): 453-61, 2005 Apr.
Article
em En
| MEDLINE
| ID: mdl-15780748
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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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Globinas
/
Deleção de Sequência
/
Talassemia beta
/
Modelos Animais de Doenças
/
Camundongos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Genomics
Assunto da revista:
GENETICA
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Austrália
País de publicação:
Estados Unidos