Transgenic animals in male reproduction research.

Abstract

Although transgenic mouse technology has already been widely used for the study of gene function and regulation in many areas of biomedicine, it has been applied only sporadically to the investigation of testicular function. Nevertheless, the contribution of this experimental approach to the understanding of male reproduction is considerable, not least because of the frequency of infertility in transgenic mice. Transgenic mice can be produced by microinjection of DNA constructs in the male pronucleus of fertilized eggs that are then retransferred into the oviducts of pseudopregnant females and allowed to develop to term. A proportion of the offspring have the foreign DNA sequences permamently integrated into the genome and thus become transgenic. In this way it is possible to obtain either the over-expression of genes, which can be targeted to the testis using testis-specific promoters, or to effect interruption of the functional integrity of genes by insertional mutagenesis. The regulation of gene expression in vivo can be studied by producing transgenic mice where the transgene is composed of the regulatory sequences of a gene of interest driving the expression of a reporter gene. Specific genes can be "knocked out" by homologous recombination. This article reviews the contribution of the transgenic approach to the following areas of male reproduction: the identification of factors involved in sex determination and development of the reproductive tract; the study of the function and expression of genes important for spermatogenesis and male reproduction; the identification of genes involved in spermatogenesis and of genomic sequences directing the expression of a transgene in the testis; the study of the function of specific reproductive tissues or cells in vivo; oncogenesis in reproductive tissues; the creation of cell lines suitable for in vitro studies; gene therapy.