Overview

Abstract

The application of transgenic and knockout (null) mouse models to the study of how specific proteins regulate gene expression—which in turn modulates cellular homeostasis, toxicology, and carcinogenesis-has become relatively routine in the last decade. Advances made in the use of these model systems are based in large part on classic research undertaken in the 1970s and 1980s, when embryologists were examining the fate of cells within early embryos and attempting to introduce exogenous DNA into mammalian embryos. It was first demonstrated in 1974 that viral DNA could be detected in mice whose blastocele cavity was injected with SV40 DNA during preimplantation development [1]. It was later shown that Moloney murine leukemia virus could be stably incorporated into the germ line of adult mice after viral infection of preimplantation mouse embryos [2]. In 1980, it was reported that pronuclear injection of exogenous DNA could integrate and be detected in somatic tissue in mice [3].