High-level erythroid expression of human alpha-globin genes in transgenic mice.
- 1 January 1989
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 86 (1) , 37-41
- https://doi.org/10.1073/pnas.86.1.37
Abstract
The human alpha 1-globin gene was fused downstream of two erythroid-specific DNase I super-hypersensitive sites that are normally located upstream of the human beta-globin locus. This construct was injected into fertilized mouse eggs, and expression was analyzed in 16-day fetal livers and brains. All 11 fetuses that contained intact copies of the transgene expressed correctly initiated human alpha-globin mRNA in the erythroid fetal liver but not in brain. Levels of expression ranged from 4% to 337% of endogenous mouse beta-globin mRNA. A human alpha-globin construct that did not contain super-hypersensitive sites was not expressed. These results demonstrate that human beta-globin locus activation sequences can stimulate high levels of human alpha-globin gene expression in erythroid tissue of transgenic mice. The results also provide a foundation for experiments designed to coexpress human alpha- and beta-globin genes in transgenic mice and suggest a feasible approach for production of a mouse model for human sickle cell disease.This publication has 28 references indexed in Scilit:
- Mouse α chains inhibit polymerization of hemoglobin induced by human or chainsBiochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology, 1988
- Position-independent, high-level expression of the human β-globin gene in transgenic miceCell, 1987
- GERM-LINE TRANSFORMATION OF MICEAnnual Review of Genetics, 1986
- Rapid reprogramming of globin gene expression in transient heterokaryonsCell, 1986
- Developmental regulation of a cloned adult β-globin gene in transgenic miceNature, 1985
- Specific expression of a foreign β-globin gene in erythroid cells of transgenic miceNature, 1985
- Regulated expression of the human β-globin gene family in murine erythroleukaemia cellsNature, 1983
- The regulated expression of β-globin genes introduced into mouse erythroleukemia cellsCell, 1983
- Expression of a β-globin gene is enhanced by remote SV40 DNA sequencesPublished by Elsevier ,1981
- The chromosomal arrangement of human α-like globin genes: Sequence homology and α-globin gene deletionsCell, 1980