Project Details
Projekt
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
Applicant
Professor Dr. Lutz Schomburg
Subject Area
Biochemistry
Term
from 2004 to 2007
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 5425310
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.
DFG Programme
Priority Programmes
Participating Person
Professor Dr. Ulrich Schweizer
