NR ASUX
AU Gonzalez,L.; Terry,L.; Jeffrey,M.J.
TI Expression of prion protein in the gut of mice infected orally with the 301V murine strain of the bovine spongiform encephalopathy agent
QU Journal of Comparative Pathology 2005 May; 132(4): 273-82
PT journal article
AB Transmissible spongiform encephalopathies (TSEs) are characterized by the accumulation of an abnormal, disease-associated prion protein (PrP(d)). Expression of its normal cellular counterpart (PrPc) by the host is a pre-requisite for the spread of infection to the central nervous system and the development of disease. Moreover, cells expressing PrPc at specific sites such as the gastrointestinal tract might be regarded as the initial point of PrPc-PrP(d) conversion after infection by the oral route. In this study, inbred mice of the I/M strain were infected orally with the 301V murine strain of the bovine spongiform encephalopathy agent. The expression of PrPc and the accumulation of PrP(d) in the intestine was then investigated immunohistochemically, together with the variations in immunoreactivity that resulted from different pretreatments of the tissue. After proteinase K (PK) pretreatment, abnormal PrP was still detectable only in the gut-associated lymphoid tissue (GALT) of clinically affected mice and, to a much more limited degree, in the enteric nervous system (ENS). Cellular PrP that disappeared after PK treatment was particularly conspicuous in the ENS and present to a lesser extent in the GALT of all mice examined after inoculation with 301V or with normal brain homogenates, as well as in uninoculated controls. These findings suggested that not all PrP found in infected mice was PrP(d) and that part of the PrP(d) was sensitive to PK treatment. Reactivity to PrP antibody 1A8 was consistently found in the absorptive epithelium of the intestinal villi, with or without PK pretreatment. However, epithelial immunolabelling was comparable in inoculated and uninoculated mice and was also consistently seen in PrP "knockout" mice used as controls. It is therefore concluded that immunohistochemically detectable accumulation of PrP(d) in the gut of mice is a relatively late event in the pathogenesis of experimental infection in this model and that the immunoreactivity observed in the intestinal epithelium does not correspond to PrP expression. While enterocytes may still play a role in the uptake of infection from the intestinal lumen, the results do not suggest that these cells are a site of initial accumulation of PrP(d).
MH Animals; Cattle; Disease Models, Animal; Encephalopathy, Bovine Spongiform/*metabolism/pathology/transmission; Endopeptidase K/pharmacology; Enterocytes/*metabolism/pathology; Immunohistochemistry; Intestines/*metabolism/pathology; Mice; Mice, Inbred Strains; Mice, Knockout; Myenteric Plexus/*metabolism/pathology; Peyer's Patches/*metabolism/pathology; Prions/administration & dosage/drug effects/genetics/*metabolism; Research Support, Non-U.S. Gov't
AD Veterinary Laboratories Agency (VLA-Lasswade), Pentlands Science Park, Midlothian EH26 0PZ, UK
SP englisch
PO England