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

硒（Se）主要以可溶性糖蛋白硒蛋白P （SePP）的形式存在于血浆中。我们通过靶向破坏SEPP基因座来产生活的SEPP - ko小鼠。这些小鼠在生长、生存、健康、生育等方面表现出复杂的表型。SePP- ko小鼠的主要特征是硒在器官中的分布改变，其他硒蛋白的表达紊乱，表明SePP具有硒载体和转运体的功能。表型表现为简单的基因-剂量关系。此外，主要的影响以性别不同的方式出现。在这里，最引人注目的例子是雄性不育和自发死亡，我们在大约30%的雄性SePP-KO小鼠中观察到。同样，雄性SePP-KO小鼠表现出更明显的生长缺陷、脂肪量减少和更明显的共济失调。这些发现指出了一个尚未解决的问题，即硒的性别特异性影响很少受到重视。因此，我们计划详细比较雄性和雌性SePP-KO小鼠的表型。雄性和雌性SePP-KO小鼠的内分泌腺受影响不同吗？基因表达是否存在性别特异性差异，从而改善了女性表型？或者当硒供应受限时，女性特有的激素/激素水平是否能保护她们免受不利影响？由于临床医学也有线索描述硒在病理生理条件下的性别特异性作用，我们相信这些研究将适合于阐明一些潜在的机制。

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.