Introduction

The use of transgenic rodents, in particular transgenic mice, to address a number of diverse biological problems has been so vast that this review chapter cannot cover every facet of transgenesis. We hope that by explaining the technology associated with the generation of transgenic mice and by focusing on a few current areas of research where transgenic animals are proving invaluable, we will help the reader understand the use of transgenic animals in research, as well as the power and limitations of this approach.

In this review a transgenic animal is defined as an animal that carries a foreign piece of DNA stably integrated into the genome of every cell in that animal. Thus, all somatic cells and the germ-cells of a transgenic animal carry the same DNA fragment at the same chromosomal location, and this DNA fragment can be transmitted in a Mendelian fashion to offspring. This DNA element is termed a transgene.

Generation of transgenic mice

There are essentially three ways of generating animals with the capacity to transmit a genetic element through the germ-line to their offspring. These are (a) retroviral integration into an early-developing embryo, (b) injection of DNA into the pronucleus of a newly fertilized egg or (c) genetic manipulation of embryonic stem cells (Fig. 5.1). All three routes have been employed to generate transgenic mice, while a few transgenic rat strains have been established chiefly through the pronuclear injection route.

Retroviral infection

If preimplantation embryos are exposed to retrovirus, a proportion of the embryonic cells will stably integrate proviral sequences into their genome, usually as one copy per cell.