Untersuchungen zur Rolle des Transkriptionsfaktors "Krueppel-like factor 4" in der Sertoli-Zelle der Maus

Krueppel-like factor (Klf4) is a zinc-finger transcription factor, which is strongly expressed in postmitotic epithelial cells of different tissues, e.g. the colon, the stomach and the skin. Klf4 is essential for the terminal differentiation of these cells and involved in the cell cycle regulation. Klf4 null mice die shortly after birth due to a loss of skin barrier function. The Krueppel-like factor 4 is also expressed in the testis: there is a high Klf4 mRNA abundance in round spermatids and Klf4 expression is strongly inducible in testicular Sertoli cells after treatment with the follicle-stimulating hormone (FSH). In order to uncover the role of this zinc-finger transcription factor in Sertoli cells we deleted Klf4 specifically in mouse Sertoli cells using the cre/loxP system. Adult mutant mice were fertile. They produced mature spermatozoa and the testicular histology appeared to be normal. So, Klf4-deficient Sertoli cells were able to support spermatogenesis in a normal range. But in the juvenile mouse testis at the time of terminal differentiation (postnatal day 18, 20) maturation of these testicular nurse cells appeared to be delayed. This was indicated by an aberrant histology of the developing testes, retarded tubular lumen formation and increased vacuolization of the Sertoli cell cytoplasms. Moreover, gene expression profiling revealed candidate genes that might provide the molecular link between the lack of Klf4 and the observed phenotype. So, Krueppel-like factor 4 is essential for Sertoli cell differentiation in the juvenile mouse testis. In a further project we characterised four different Klf4 transcripts in the mouse testis and showed that they were generated by the usage of alternative polyadenylation signals. Moreover we analysed the expression profile of the Klf4 mRNA and protein in a Sertoli cell line, demonstrated that Klf4 strongly responds within a few minutes to a Forskolin stimulus and therefore classified Klf4 as an immediate early response gene.