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High-level erythroid expression of human alpha-globin genes in transgenic mice.
Author(s) -
Thomas M. Ryan,
Richard R. Behringer,
Tim M. Townes,
Richard D. Palmiter,
Ralph L. Brinster
Publication year - 1989
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.86.1.37
Subject(s) - locus control region , globin , transgene , biology , microbiology and biotechnology , genetically modified mouse , gene , locus (genetics) , alpha (finance) , gene expression , alpha globulin , messenger rna , beta (programming language) , genetics , promoter , medicine , construct validity , nursing , computer science , patient satisfaction , programming language
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.

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