A humanized BAC transgenic/knockout mouse model for HbE/β-thalassemia
| Autor: | Heidi Peters, Robert Williamson, Lucille Voullaire, Sophie Gazeas, Faten Zaibak, Jim Vadolas, Kerry J. Fowler, Panayiotis A. Ioannou, Suthat Fucharoen, Duangporn Jamsai |
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| Jazyk: | angličtina |
| Předmět: |
Genetically modified mouse
Transgene Thalassemia Gene Dosage HbF induction Mice Transgenic Biology Southeast asian Mice medicine Genetics Animals Humans Point Mutation Transgenes Point mutation Hemoglobin E beta-Thalassemia BAC transgenic mice medicine.disease β-Thalassemia Null allele Molecular biology Disease Models Animal Phenotype Knockout mouse |
| Zdroj: | Genomics. (3):309-315 |
| ISSN: | 0888-7543 |
| DOI: | 10.1016/j.ygeno.2006.03.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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