Retroviral vector sequences inhibit human beta-globin gene expression in transgenic mice.
The DNase I hypersensitive site 5' HS2 of the human beta-globin locus control region confers position-independent, high-level expression on the human beta-globin gene in transgenic mice. When a 5' HS2 beta-globin construct is flanked by retroviral vector sequences derived from Moloney Murine Leukemia Virus (MoMLV), expression of the beta-globin gene is severely inhibited. Apparently, one or more elements within the MoMLV genome is capable of repressing transcription of the human beta-globin gene in transgenic mice. A construct lacking the retroviral enhancer also fails to express the beta-globin gene, indicating that this region of the virus is not essential for repression. Further analysis may permit the identification of specific viral sequences that inhibit gene expression; these sequences could then be deleted or mutated to produce improved viral vectors.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Alabama at Birmingham 35294.
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Townes
D000818:Animals; D015139:Blotting, Southern; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005914:Globins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008845:Microinjections; D008979:Moloney murine leukemia virus / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic
D005914:Globins; D003850:Deoxyribonuclease I