Late Stage Cathepsin C, CXCL13 and Ki-67 Overexpression Correlate with Regional Neuropathology in a BSE Transgenic Murine Model

SummaryA DNA microarray-based gene expression analysis study was performed with bovine spongiform encephalopathy (BSE) transgenic mice. Several genes were found to be overexpressed including the lysosomal enzyme cathepsin C, the chemokine CXCL13 and a number of genes related to cellular proliferation. The brains from terminal stage, BSE inoculated, ‘bovinized’, transgenic mice were subjected to immunohistochemistry with antibodies against these two proteins and Ki-67, a cell proliferation marker, to assess the biological relevance of the gene expression changes. Differential expression of cathepsin C and CXCL13 proteins and increased expression of Ki-67 was observed. These changes were localized to areas of deposition of PrPres and spongiform change and to areas showing an astroglial and microglial response. These findings suggest that these proteins are involved in the mechanisms leading to the establishment of transmissible spongiform encephalopathy.