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| Content Provider | Springer Nature Link |
|---|---|
| Author | Al Hasani, Keith Vadolas, Jim Knaupp, Anja S. Wardan, Hady Voullaire, Lucille Williamson, Robert Ioanu, Panayiotis A. |
| Copyright Year | 2005 |
| Abstract | A 191-kb human bacterial artificial chromosome (BAC) containing the human α-globin genomic locus was used to generate transgenic mice that express, exclusively, human α-globin (huα-globin). Expression of huα-globin reaches a level of 36% of that of endogenous mouse α-globin (muα-globin) on a heterozygous mouse α-thalassemia background (muα-globin knockout, muα+/−). Hemizygous transgenic mice carrying the huα-globin locus on a heterozygous knockout background (huα+/0, muα++/−−) demonstrated complementation of most hematologic parameters. By crossing huα+/0, muα++/−− mice, we were able to generate mice entirely dependent on huα-globin synthesis. Breeding and fluorescent in situ hybridization studies demonstrate that only mice homozygous for the transgene were able to rescue embryonic lethal homozygous muα-globin knockout embryos (muα−−/−−). Adult rescued mice produce hemoglobin at levels similar to wild-type mice, with partial red cell complementation based on mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and red cell distribution width (RDW) measurements. Significant erythrocythemia above wild-type levels seems to be the main compensatory mechanism for the normalization of the hemoglobin levels in the rescued animals. Our studies demonstrate that the huα-globin locus in the 191-kb transgene contains all the necessary elements for the regulated expression of huα-globin in transgenic mice. This animal model should be valuable for studying the mechanisms regulating huα-globin production and for development of therapeutic strategies for β-thalassemia based on downregulation of α-globin expression. |
| Starting Page | 847 |
| Ending Page | 853 |
| Page Count | 7 |
| File Format | |
| ISSN | 09388990 |
| Journal | Mammalian Genome |
| Volume Number | 16 |
| Issue Number | 11 |
| e-ISSN | 14321777 |
| Language | English |
| Publisher | Springer-Verlag |
| Publisher Date | 2005-11-11 |
| Publisher Place | New York |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Anatomy Cell Biology Zoology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
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