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Absence of selenoprotein p but not selenocysteine lyase results in neurological dysfunction in mice
Author(s) -
Raman Arjun,
Pitts Matthew,
Seyedali Ali,
Hashimoto Ann,
Seale Lucia,
Bellinger Frederick,
Berry Marla
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb135
Subject(s) - selenocysteine , selenoprotein , selenoprotein p , genetically modified mouse , knockout mouse , transgene , medicine , endocrinology , biology , glutathione peroxidase , neuroscience , enzyme , biochemistry , oxidative stress , gene , catalase , receptor , cysteine
Selenium (Se) is a trace element that is important for the mammalian central nervous system (CNS). Selenoprotein P (Sepp1) is a Se‐rich protein that is important for brain Se supply, and is thought to supply Se via the enzyme selenocysteine lyase (Scly). Sepp1‐deficient mice develop neurological symptoms of spasticity, and have deficient synaptic plasticity and spatial learning. In this study, male and female transgenic mice lacking Sepp1 or Scly on variable Se diets were evaluated using behavioral and biochemical paradigms for neurological dysfunction. Male mice lacking Sepp1 appear worse than age‐matched female mice, suggesting that males have a higher demand for Sepp1 and Se in the CNS than females. Surprisingly, no behavioral impairment was observed in mice lacking Scly unless they were restricted with a low Se diet. Se deficiency uncovered a mild learning disruption in Scly knockout mice without causing motor deficits. Scly‐deficient mice fed a low Se diet display reduced expression and activity of selenoproteins in brain. These results suggest that Sepp1 is more critical than Scly for CNS function and maintenance of brain Se, but that both gene products are physiologically relevant during dietary Se deficiency. This research was supported by NIH grants RR003061, DK047320, RR016467 and DA027318.