Lack of influence of prion protein gene expression on kainate-induced seizures in mice: studies using congenic, coisogenic and transgenic strains

Neuroscience. 2013 May 15;238:11-8. doi: 10.1016/j.neuroscience.2013.02.004. Epub 2013 Feb 13.

Abstract

Prion protein (PrP) is a glycosylphosphatidylinositol (GPI) anchored cell surface protein expressed by many cells, including those of the mammalian nervous system. At present the physiologic functions of PrP remain unclear. Deletion of Prnp, the gene encoding PrP in mice, has been shown to alter normal synaptic and electrophysiologic activities, indicating a potential role in seizure susceptibility. However, published efforts to link PrP with seizures, using both in vivo and in vitro models, are conflicting and difficult to interpret due to use of various mouse backgrounds and seizure induction techniques. Here we investigated the role of PrP in kainic acid (KA)-induced seizure sensitivity, using three types of mice. In contrast to previous published results, Prnp-/- mice on the C57BL/10SnJ background had a significant decrease in KA-induced seizure susceptibility. In genetic complementation experiments using a PrP-expressing transgene, genes derived from strain 129/Ola, which flanked the Prnp-/- locus in C57BL/10SnJ mice, rather than Prnp itself, appeared to account for this effect. Furthermore, using coisogenic 129/Ola mice differing only at Prnp, this difference was not reproduced when comparing PrP-negative and PrP-positive mice. In contrast, substrains of PrP-expressing C57BL mice, showed large variations in KA-induced seizure sensitivity. The magnitude of these differences in susceptibility was larger than that associated with the presence of the Prnp gene, suggesting extensive influence of genes other than Prnp on seizure sensitivity in this system.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Gene Expression*
  • Genetic Predisposition to Disease
  • Kainic Acid
  • Mice
  • Mice, Transgenic
  • Neurons / metabolism*
  • Prions / genetics*
  • Prions / metabolism
  • Seizures / chemically induced
  • Seizures / genetics*
  • Seizures / metabolism
  • Species Specificity

Substances

  • Prions
  • Kainic Acid