Gene Expression in the Medulla Following Oral Infection of Cattle with Bovine Spongiform Encephalopathy

Abstract

The identification of variations in gene expression in response to bovine spongiform encephalopathy (BSE) may help to elucidate the mechanisms of neuropathology and prion replication and discover biomarkers for disease. In this study, genes that are differentially expressed in the caudal medulla tissues of animals infected with different doses of PrP^BSE at 12 and 45 mo post infection were compared using array containing 24,000 oligonucleotide probes. Data analysis identified 966 differentially expressed (DE) genes between control and infected animals. Genes identified in at least two of four experiments (control versus 1-g infected animals at 12 and 45-mo; control versus 100-g infected animals at 12 and 45 mo) were considered to be the genes that may be associated with BSE disease. From the 176 DE genes associated with BSE, 84 had functions described in the Gene Ontology (GO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 14 genes revealed that prion infection may cause dysfunction of several different networks, including extracellular matrix (ECM), cell adhesion, neuroactive ligand–receptor interaction, complement and coagulation cascades, MAPK signaling, neurodegenerative disorder, SNARE interactions in vesicular transport, and the transforming growth factor (TGF) beta signaling pathways. The identification of DE genes will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species. Additional studies on larger number of animals are in progress in our laboratory to investigate the roles of these DE genes in pathogenesis of BSE.

Acknowledgments

This research was supported by PrionNet Canada, Alberta Prion Institute and Alberta Bovine Genomic Program. We thank the Veterinary Laboratories Agency (Weybridge, UK) for providing the tissue samples to prepare RNA used in this study (funded by Defra project SE1736 and EU project FAIR CT98-778). JLW thanks the Cariplo Foundation for its support.

Current address for Masaaki Taniguchi is Animal Genome Research Unit, National Institute of Agrobiological Sciences, 2 Ikenodai, Tsukuba, Japan.