Physiological effects of altered Se transport and Se tissue distribution in selenoprotein P knock out mice - studies on the impact of gender on the phenotype

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Selenium (Se) is mainly contained in plasma within a soluble glycoprotein, i.e. selenoprotein P (SePP). We generated viable SePP-KO mice by targeted disruption of the SEPP locus. These mice display a complex phenotype with respect to growth, survival, fitness, fertility, etc. SePP-KO mice are mainly characterized by an altered Se-distribution among the organs and by disturbed expression of the other selenoproteins indicating that SePP functions as a Se-carrier and -transporter. The phenotype displays a simple gene-dose relationship. Moreover, the major effects emerged in a gender-specific manner. Here, the most striking examples were male infertility and spontaneous fatalities that we observed in around 30% of male SePP-KO mice. Likewise male SePP-KO mice displayed more pronounced growth defects, reduced fat mass and more pronounced ataxia. These findings point to an unresolved issue, i.e. sex-specific effects of Se that have rarely received major attention, yet. Thus we plan to compare the phenotype of male and female SePP-KO mice in detail. Are the endocrine glands affected differently in male and female SePP-KO mice? Are there gender-specific differences in gene expression that ameliorate the female phenotype? Or do female-specific hormones/hormone-levels protect from the adverse effects that arise when the Se supply is limiting? Since there are also hints from clinical medicine describing gender-specific effects of Se in pathophysiological conditions, we believe that these studies will be suited to clarify some of the underlying mechanisms.