EXPRESSION OF TRANSDUCED GENES IN MICE GENERATED BY INFECTING BLASTOCYSTS WITH AVIAN-LEUKOSIS VIRUS-BASED RETROVIRAL VECTORS

Transgenic mouse lines have been developed that express the tv-a recep tor under the control of the chicken beta-actin promoter. These mice e xpress the tv-a receptor in most or all tissues and in the early embry o. An avian leukosis virus (ALV)-based retroviral vector system was us ed for the efficient delivery of genes into preimplantation mouse embr yos from these transgenic lines. Experimental animals could be generat ed quickly and easily by infecting susceptible blastocysts with ALV-ba sed retroviral vectors. Expression of the delivered genes was controll ed by either the constitutive viral promoter contained in the long ter minal repeat or an internal nonviral tissue-specific promoter. Mating the infected founder chimeric animals produced animals that carry the ALV provirus as a transgene. A subset of the integrated proviruses exp ressed the chloramphenicol acetyltransferase reporter gene from either the promoter in the long terminal repeat or an internal promoter, whi ch we believe indicates that many of the sites that are accessible to viral DNA insertion in preimplantation embryos are incompatible with e xpression in older animals. This approach should prove useful for stud ies on murine cell lineage and development, providing models for study ing oncogenesis, and testing gene therapy strategies.