Transgenic mice as a model to study the regulation of human transferrin expression in Sertoli cells.

Abstract

Understanding the regulation of proteins secreted by human Sertoli cells is important for identifying the causes of infertility in men. However, experiments with Sertoli cells purified from healthy testes are difficult to perform, for obvious ethical reasons. Therefore, experiments with transgenic mouse models could provide an alternative approach to study the function and regulation of a human gene in Sertoli cells. To validate this approach, transgenic mice were generated using phage P1 containing an 80 kbp insert encompassing the complete human transferrin (hTf) gene. The expression pattern of hTf in the mouse background was analysed by isolating Sertoli cells from transgenic mice and comparing the regulation of the human and mouse Tf genes by hormones, retinoids and a cytokine in vitro. The hTf gene in transgenic mice shows a tissue-specific expression pattern that mimics the pattern observed in the human. In Sertoli cell cultures, FSH, insulin, retinol or tumour necrosis factor-alpha (TNF-alpha) stimulated hTf secretion, while testosterone alone had no effect. A combination of FSH, insulin, retinol and testosterone or a combination of TNF-alpha and retinol stimulated hTf secretion, but no additive effect was observed. Besides their well-known advantages, transgenic mice seem to be useful models to recapitulate the normal regulation of a human gene.