A humanized mouse model for a common beta0-thalassemia mutation.
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.
Jamsai
Duangporn
D
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.
Zaibak
Faten
F
Khongnium
Wantana
W
Vadolas
Jim
J
Voullaire
Lucille
L
Fowler
Kerry J
KJ
Gazeas
Sophie
S
Fucharoen
Suthat
S
Williamson
Robert
R
Ioannou
Panayiotis A
PA
D000818:Animals; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000002:abnormalities; D004913:Erythrocytes, Abnormal / Q000166:cytology; D015870:Gene Expression; D005914:Globins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051379:Mice / Q000235:genetics*; D018345:Mice, Knockout; D010641:Phenotype; D017384:Sequence Deletion; D019076:Transgenes; D017086:beta-Thalassemia / Q000235:genetics*
D005914:Globins