Progress on low susceptibility mechanisms of transmissible spongiform encephalopathies

Transmissible spongiform encephalopathies （TSEs）, also known as prion diseases, are a group of fatal neurodegenerative diseases detected in a wide range of mammalian species. The ＂protein-only＂ hypothesis of TSE suggests that prions are transmissible particles devoid of nucleic acid and the primary pathogenic event is thought to be the conversion of cellular prion protein （PrPc） into the disease-associated isoform （prpSc）. According to susceptibility to TSEs, animals can be classified into susceptible species and low susceptibility species. In this review we focus on several species with low susceptibility to TSEs： dogs, rabbits, horses and buffaloes. We summarize recent studies into the characteristics of low susceptibility regarding protein structure, and biochemical and genetic properties.

Expression of BSE-associated proteins in the CNS and lymphoreticular tissues of cattle and buffalo

Bovine spongiform encephalopathy(BSE),which has been documented in 190,000 cases of BSE-infected cattle,to our knowledge,has not been reported in buffalo.Prion protein(PrP) is critical to susceptibility and development of BSE.Moreover,a new PrP-like protein,Shadoo(Sho),has been shown to have overlapping expression patterns and shared functions with PrP.Therefore,we hypothesize that differences in expression at the transcriptional level and/or the post-transcriptional level of the two genes may be associated with these specific differences between cattle and buffalo.We compared the relative mRNA expression of the prion protein gene(PRNP) and the Shadoo gene(SPRN) in 3% RNA samples using real-time PCR.We also analyzed PrP/Sho protein from 96 samples by Western blot.Our results demonstrated significantly lower PrP expression in the cerebellum,obex,mesenteric lymph node,and bronchial lymph node tissues,but higher relative expression of Sho in the cerebrum and spleen in buffalos compared with catties.Although these results support our primary assumption,Sho and PrP expressions did not correlate with corresponding mRNA expression,suggesting that the biological modulations of both PrP and Sho proteins are at post-translational levels.Moreover,positive correlations between PRNP and SPRN were found in cattle and buffalo cerebrum as well as in buffalo obex.Conversely,negative correlations between PrP and Sho were detected in buffalo cerebellum and obex tissues.These findings suggest that additional post-transcriptional studies are warranted to elucidate mechanisms behind prion diseases.