title: A humanized mouse model for a common beta0-thalassemia mutation.
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.
authors.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.
authors.forename: Duangporn
authors.initials: D
authors.lastname: Jamsai
authors.forename: Faten
authors.initials: F
authors.lastname: Zaibak
authors.forename: Wantana
authors.initials: W
authors.lastname: Khongnium
authors.forename: Jim
authors.initials: J
authors.lastname: Vadolas
authors.forename: Lucille
authors.initials: L
authors.lastname: Voullaire
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Fowler
authors.forename: Sophie
authors.initials: S
authors.lastname: Gazeas
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Robert
authors.initials: R
authors.lastname: Williamson
authors.forename: Panayiotis A
authors.initials: PA
authors.lastname: Ioannou
mesh_terms: 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*
chemical_list: D005914:Globins