Spontaneous Germ-Line Ecotropic Murine Leukemia Virus Infection: Implications for Retroviral Insertional Mutagenesis and Germ-Line Gene Transfer

Ecotropic murine leukemia viruses (MuLWs) provide important tools for the study of mammalian development. Not only can they act as germ-line insertional mutagens, facilitating the identification and cloning of genes important in mammalian development, but they can also serve as vectors for the efficient delivery of genes into mammalian cells. This chapter presents implications for retroviral insertional mutagenesis and germ-line gene transfer. The development of inbred and/or hybrid strains of mice that spontaneously acquire new germ-line proviruses at high frequencies provide a technically simple experimental system for viral insertional mutagenesis and may ultimately allow for selected mutagenesis similar to what is now being done in Drosophila melanogaster with P elements. The development of such system has, however, been hindered by the low frequency at which ecotropic proviruses are spontaneously acquired in the mouse germ line. The identification of a hybrid mouse strain combination, SWR/J-RF/J, that has high frequencies of spontaneous provirus acquisition has enabled the execution of experiments designed to delineate the mechanism and developmental stage of provirus acquisition and to evaluate the potential of this approach for retroviral insertional mutagenesis. The results of these experiments have important implications for the use of retroviral vectors to introduce foreign genes into the germ line of mice and other mammalian species.