Involvement of PrPC in kainate-induced excitotoxicity in several mouse strains

The cellular prion protein (PrP C) has been associated with a plethora of cellular functions ranging from cell cycle to neuroprotection. Mice lacking PrP C show an increased susceptibility to epileptic seizures; the protein, then, is neuroprotective. However, lack of experimental reproducibility has led to considering the possibility that other factors besides PrP C deletion, such as the genetic background of mice or the presence of so-called â Prnp flanking genesâ € might contribute to the reported susceptibility. Here, we performed a comparative analysis of seizure-susceptibility using characterized Prnp +/+ and Prnp 0/0 mice of B6129, B6.129, 129/Ola or FVB/N genetic backgrounds. Our study indicates that PrP C plays a role in neuroprotection in KA-treated cells and mice. For this function, PrP C should contain the aa32-93 region and needs to be linked to the membrane. In addition, some unidentified â Prnp-flanking genesâ €play a role parallel to PrP C in the KA-mediated responses in B6129 and B6.129 Prnp 0/0 mice.

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Bibliographic Details
Main Authors: Carulla, P., Llorens, F., Matamoros-Angles, A., Aguilar-Calvo, P., Espinosa Cores, María Loreto, Gavín, R., Ferrer, I., Legname, G., Torres, J. M., Del Río, J. A.
Format: artículo biblioteca
Language:English
Published: Nature Research 2015
Online Access:http://hdl.handle.net/20.500.12792/4969
http://hdl.handle.net/10261/290095
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Summary:The cellular prion protein (PrP C) has been associated with a plethora of cellular functions ranging from cell cycle to neuroprotection. Mice lacking PrP C show an increased susceptibility to epileptic seizures; the protein, then, is neuroprotective. However, lack of experimental reproducibility has led to considering the possibility that other factors besides PrP C deletion, such as the genetic background of mice or the presence of so-called â Prnp flanking genesâ € might contribute to the reported susceptibility. Here, we performed a comparative analysis of seizure-susceptibility using characterized Prnp +/+ and Prnp 0/0 mice of B6129, B6.129, 129/Ola or FVB/N genetic backgrounds. Our study indicates that PrP C plays a role in neuroprotection in KA-treated cells and mice. For this function, PrP C should contain the aa32-93 region and needs to be linked to the membrane. In addition, some unidentified â Prnp-flanking genesâ €play a role parallel to PrP C in the KA-mediated responses in B6129 and B6.129 Prnp 0/0 mice.