Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2007) 14 P183

ECE2007 Poster Presentations (1) (659 abstracts)

Selenium supply modulates growth spurt of selenoprotein P knockout mice

Kostja Renko , Marten Michaelis , Ulrich Schweizer , Josef Köhrle & Lutz Schomburg

Institut für Experimentelle Endokrinologie, Charité Universitätsmedizin Berlin, Berlin, Germany.

Background: Selenoproteins are playing an important role in body homeostasis and development. They control thyroid hormone metabolism and are of prime importance for intracellular redox regulation and cellular defence. The SePP knockout mouse (SePP-KO) is a model of impaired Se metabolism characterized by a disrupted distribution system for organified Se. One of the major phenotypes of the homozygote SePP-KO mice is a reduced increase in size and weight during the growth spurt that can dose-dependently be rescued by Se supplementation.

Hypothesis: Se has an effect on the growth hormone axis and affects bone metabolism by modifying either growth signal synthesis or the response of target tissues.

Materials and methods: Male and female wild-type, heterozygous and homozygous SePP-KO mice were raised on regular rodent chow. At the age of 35 days, we studied the expression of growth-relevant genes in target tissues by realtime-PCR and Nothern blot analysis. Serum markers like IGF-1 and Leptin were determined by multiplex ELISA technique.

Results: On commercial diets with Se-contents not specified, we identified disarrangements in the IGF- and IGFBP-mRNA expression levels, which appeared inconclusive. On diets with defined Se content, male SePP-KO mice had a body weight of 11.3 g (±0.4 g) at P35 compared to 14.8 g (±0.6 g) in heterozygous or wild-type mice (P<0.001). The diets revealed a narrow window between rescue (above 0.24 ppm Se) and lethal progression of the phenotype (below 0.15 ppm). These findings now result in a well-defined model to study the impact of Se on growth and body mass.

Conclusion: Se metabolism, Se status and Se transport have an important impact on growth and body mass. Different SePP expression levels modify growth and development in transgenic SePP-KO mice. Together with specific diets this mouse model offers an ideal way to study the interaction of Se supply and growth hormone axis.

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