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Nucleic Acids Research, 1994, Vol. 22, No. 21 4477-4481
© 1994

MOLECULAR BIOLOGY

Retroviral vector sequences inhibit human ß-globin gene expression in transgenic mice

Steven L. McCune and Tim M. Townes*

Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Brimingham Birmingham, AL 35294, USA

*To whom correspondence should be addressed

Received July 19, 1994. Revised September 15, 1994. Accepted September 15, 1994.

The DNase I hypersensitive site 5' HS2 of the human ß-globin locus control region confers positionindependent, high-level expression on the human ß- globin gene in transgenic mice. When a 5' HS2 ß-globin construct is flanked by retroviral vector sequences derived from Moloney Murine Leukemia Virus (MoMLV), expression of the ß-globin gene is severely inhibited. Apparently, one or more elements within the MoMLV genome is capable of repressing transcription of the human ß-globin gene in transgenic mice. A construct lacking the retroviral enhancer also fails to express the ß-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.


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