TRANSGENIC ANIMALS IN MALE REPRODUCTION RESEARCH

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 testic ular function. Nevertheless, the contribution of this experimental app roach to the understanding of male reproduction is considerable, not l east because of the frequency of infertility in transgenic mice. Trans genic mice can be produced by microinjection of DNA constructs in the male pronucleus of fertilized eggs that are then retransferred into th e oviducts of pseudopregnant females and allowed to develop to term. A proportion of the offspring have the foreign DNA sequences permanentl y integrated into the genome and thus become transgenic. In this way i t is possible to obtain either the over-expression of genes, which can be targeted to the testis using testis-specific promoters, or to effe ct interruption of the functional integrity of genes by insertional mu tagenesis. The regulation of gene expression in vivo can be studied by producing transgenic mice where the transgene is composed of the regu latory sequences of a gene of interest driving the expression of a rep orter gene. Specific genes can be ''knocked out'' by homologous recomb ination. This article reviews the contribution of the transgenic appro ach to the following areas of male reproduction: the identification of factors involved in sex determination and development of the reproduc tive tract; the study of the function and expression of genes importan t for spermatogenesis and male reproduction; the identification of gen es 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 reprodu ctive tissues; the creation of cell lines suitable for in vitro studie s; gene therapy.