Document Detail

A humanized BAC transgenic/knockout mouse model for HbE/beta-thalassemia.
MedLine Citation:
PMID:  16631345     Owner:  NLM     Status:  MEDLINE    
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.
Duangporn Jamsai; Faten Zaibak; Jim Vadolas; Lucille Voullaire; Kerry J Fowler; Sophie Gazeas; Heidi Peters; Suthat Fucharoen; Robert Williamson; Panayiotis A Ioannou
Related Documents :
22223845 - Monosodium glutamate-induced diabetic mice are susceptible to azoxymethane-induced colo...
3838975 - Hemoglobin kenitra alpha 2 beta 2 69 (e13) gly----arg. a new beta variant of elevated e...
24501175 - Gpi-anchored protein complex, ly6k/tex101, is required for sperm migration into the ovi...
2117325 - Aberrance and modification of alpha-1- and alpha-2-globin gene expression in human and ...
22808845 - Elimination of alpha-gal xenoreactive epitope: alpha-galactosidase treatment of porcine...
15239085 - Beyond insulin resistance in nash: tnf-alpha or adiponectin?
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    
Cell and Gene Therapy Research Group, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, VIC 3052, Australia.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Disease Models, Animal
Gene Dosage*
Hemoglobin E / genetics*
Mice, Transgenic
Point Mutation*
beta-Thalassemia / genetics*,  pathology,  therapy
Reg. No./Substance:
9034-61-1/Hemoglobin E

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

Previous Document:  A novel RNAi library based on partially randomized consensus sequences of nuclear receptors: identif...
Next Document:  Expression of insulin-like growth factor-2 receptors on EL4 lymphoma cells overexpressing growth hor...