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Immunoreactivity to ubiquitin—protein conjugates is present early in the disease process in the brains of scrapie‐infected mice
Author(s) -
Lowe James,
Fergusson Jill,
Kenward Nigel,
Laszlo Lajos,
Landon Michael,
Farquhar Christine,
Brown John,
Hope James,
Mayer R. John
Publication year - 1992
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1711680204
Subject(s) - immunogold labelling , scrapie , biology , ubiquitin , immunocytochemistry , lysosome , pathology , pathological , virology , antibody , blot , prion protein , disease , immunology , gene , medicine , genetics , enzyme , biochemistry
Brains from mice infected with either the 87V or the ME7 strains of mouse‐passaged sheep scrapie were taken at stages during the disease process and immunostained to show the localization of ubiquitin‐protein conjugates. In both models, conjugates were seen as fine, dot‐like structures; as coarser, granular lesions within or adjacent to neurones; and in areas surrounding plaques. The dot‐like structures were visible at 28 days post‐ME7 infection and at 55 days in 87V‐infected mice. In both models, the extent of immunoreactive changes increased as the disease progressed and terminal infection was as described earlier by us (Lowe et al., J. Pathot 1990; 162 : 61–66). The patterns of development of these features were distinctive in two ways: progression from region to region was observable and the density of the pathological lesions grew exponentially as the clinical symptoms appeared. The earliest pathological dot‐like structures corresponded temporally with the earliest detection of PrP sc by Western blotting, and immunogold electron microscopic investigation of the dot‐like lesions indicated that they were the multi‐vesicular, lysosome‐related, dense bodies that we have described previously in terminal disease (Laszlo et al., J Pathol 1992; 166 : 333–341). Until now, ubiquitin–protein conjugates were seen mainly in inclusion bodies associated with the terminal stages of a range of human degenerative diseases. This study establishes that ubiquitin–protein conjugates accumulate in lysosome‐related bodies very early and appear to be intimately related to the pathological processes in the animal disorders that we have studied.