RETROVIRAL VECTOR SEQUENCES INHIBIT HUMAN BETA-GLOBIN GENE-EXPRESSIONIN 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-glob in construct is flanked by retroviral vector sequences derived from Mo loney Murine Leukemia Virus (MoMLV), expression of the beta-globin gen e is severely inhibited. Apparently, one or more elements within the M oMLV genome is capable of repressing transcription of the human beta-g lobin gene in transgenic mice. A construct lacking the retroviral enha ncer 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.