Microarray Analysis of Differentially Expressed Genes from Peyer's Patches of Cattle Orally Challenged with Bovine Spongiform Encephalopathy

Abstract

The most likely route of entry of infection following oral exposure to transmissible spongiform encephalopathies (TSE) is via the immunologically active Peyer's patches (PP). These secondary lymphoid organs appear to be the potential route for prion neuroinvasion. However, the molecular mechanisms involved in the uptake of the infectious prion agent and progression of disease remain still unclear. This investigation examined the changes in gene expression in PP following oral exposure of cattle to bovine spongiform encephalopathy (BSE) agents. The gene expression patterns in PP from cows 12 mo after BSE challenge were compared with controls using a microarray platform containing 24,000 oligonucleotides representing 16,846 unique gene loci and 5943 Expressed Sequence Tag (EST) from bovine genome. Between the challanged and control animals, 90 genes and 16 EST were identified as significantly differentially, expressed (>2.0-fold change): 36 were upregulated and 70 were downregulated. Of these genes, five were found to be related to immune function. Major histocompatibility complex (MHC) class II, MHC class II DQ alpha, L-RAP, and two hypothetical proteins. Differentially expressed genes related to cellular and metabolic processes including development and maturation of cells in the PP were also identified. In this context, the potential impacts of these gene expression changes in PP on BSE development are discussed.

Acknowledgements

PrioNet Canada and Alberta Prion Research Institute are acknowledged for funding this project. The authors also acknowledge Veterinary Laboratories Agency (VLA), Weybridge, UK, for collecting, processing, and supplying the samples.

Current address for Masaaki Tanigushi is Animal Genome Research Unit, Division of Animal Sciences, National Institute of Agrobiological Sciences, 2 Ikenodai, Tsukuba, Ibaraki 305–8602, Japan.