Document Detail


A humanized BAC transgenic/knockout mouse model for HbE/beta-thalassemia.
MedLine Citation:
PMID:  16631345     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hemoglobin E (HbE) is caused by a G-->A mutation at codon 26 of the beta-globin gene, which substitutes Glu-->Lys. This mutation gives rise to functional but unstable hemoglobin and activates a cryptic splice site causing mild anemia. HbE reaches a carrier frequency of 60-80% in some Southeast Asian populations. HbE causes serious disease when co-inherited with a beta-thalassemia mutation. In this study, we report the creation and evaluation of humanized transgenic mice containing the beta(E) mutation in the context of the human beta-globin locus. Developmental expression of the human beta(E) locus transgene partially complements the hematological abnormalities in heterozygous knockout mice ((mu)beta(th-3/+)) and rescues the embryonic lethality of homozygous knockout mice ((mu)beta(th-3/th-3)). The phenotype of rescued mice was dependent on the transgene copy number. This mouse model displays hematological abnormalities similar to HbE/beta-thalassemia patients and represent an ideal in vivo model system for pathophysiological studies and evaluation of novel therapies.
Authors:
Duangporn Jamsai; Faten Zaibak; Jim Vadolas; Lucille Voullaire; Kerry J Fowler; Sophie Gazeas; Heidi Peters; Suthat Fucharoen; Robert Williamson; Panayiotis A Ioannou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-02
Journal Detail:
Title:  Genomics     Volume:  88     ISSN:  0888-7543     ISO Abbreviation:  Genomics     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-28     Completed Date:  2006-10-31     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8800135     Medline TA:  Genomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  309-15     Citation Subset:  IM    
Affiliation:
Cell and Gene Therapy Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia. duangporn.jamsai@med.monash.edu.au
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MeSH Terms
Descriptor/Qualifier:
Animals
Disease Models, Animal
Gene Dosage*
Hemoglobin E / genetics*
Humans
Mice
Mice, Transgenic
Phenotype
Point Mutation*
Transgenes*
beta-Thalassemia / genetics*,  pathology,  therapy
Chemical
Reg. No./Substance:
9034-61-1/Hemoglobin E

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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