Research
Central nervous system gene expression changes in a transgenic mouse model for bovine spongiform encephalopathy
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* Corresponding author: Raül Tortosa raul.tortosa@vhir.org
1 Departament de Medicina i Cirurgia Animals, Universitat Autònoma de Barcelona, 08193, Cerdanyola del Vallès, Barcelona, Spain
2 Institut de Biotecnologia i Biomedicina i Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
3 Priocat Laboratory, Centre de Recerca en Sanitat Animal, UAB-IRTA, Campus de la Universitat Autònoma de Barcelona, 08193, Barcelona, Spain
4 Departament d'Estadística, Facultat de Biologia, Universitat de Barcelona, 08028 Barcelona, Spain
5 Centro de Investigación en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid, Spain
6 Centre de Biotecnologia Animal i de Teràpia Gènica (CBATEG), Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain
Veterinary Research 2011, 42:109 doi:10.1186/1297-9716-42-109
Published: 28 October 2011Abstract
Gene expression analysis has proven to be a very useful tool to gain knowledge of the factors involved in the pathogenesis of diseases, particularly in the initial or preclinical stages. With the aim of finding new data on the events occurring in the Central Nervous System in animals affected with Bovine Spongiform Encephalopathy, a comprehensive genome wide gene expression study was conducted at different time points of the disease on mice genetically modified to model the bovine species brain in terms of cellular prion protein. An accurate analysis of the information generated by microarray technique was the key point to assess the biological relevance of the data obtained in terms of Transmissible Spongiform Encephalopathy pathogenesis. Validation of the microarray technique was achieved by RT-PCR confirming the RNA change and immunohistochemistry techniques that verified that expression changes were translated into variable levels of protein for selected genes. Our study reveals changes in the expression of genes, some of them not previously associated with prion diseases, at early stages of the disease previous to the detection of the pathological prion protein, that might have a role in neuronal degeneration and several transcriptional changes showing an important imbalance in the Central Nervous System homeostasis in advanced stages of the disease. Genes whose expression is altered at early stages of the disease should be considered as possible therapeutic targets and potential disease markers in preclinical diagnostic tool development. Genes non-previously related to prion diseases should be taken into consideration for further investigations.