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Ultrastructure and pathology of prion protein amyloid accumulation and cellular
damage in extraneural tissues of scrapie-infected transgenic mice expressing
anchorless prion protein
#MMPMID28759310
Race B
; Jeffrey M
; McGovern G
; Dorward D
; Chesebro B
Prion
2017[Jul]; 11
(4
): 234-248
PMID28759310
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In most human and animal prion diseases the abnormal disease-associated prion
protein (PrPSc) is deposited as non-amyloid aggregates in CNS, spleen and
lymphoid organs. In contrast, in humans and transgenic mice with PrP mutations
which cause expression of PrP lacking a glycosylphosphatidylinositol
(GPI)-anchor, most PrPSc is in the amyloid form. In transgenic mice expressing
only anchorless PrP (tg anchorless), PrPSc is deposited not only in CNS and
lymphoid tissues, but also in extraneural tissues including heart, brown fat,
white fat, and colon. In the present paper, we report ultrastructural studies of
amyloid PrPSc deposition in extraneural tissues of scrapie-infected tg anchorless
mice. Amyloid PrPSc fibrils identified by immunogold-labeling were visible at
high magnification in interstitial regions and around blood vessels of heart,
brown fat, white fat, colon, and lymphoid tissues. PrPSc amyloid was located on
and outside the plasma membranes of adipocytes in brown fat and cardiomyocytes,
and appeared to invaginate and disrupt the plasma membranes of these cell types,
suggesting cellular damage. In contrast, no cellular damage was apparent near
PrPSc associated with macrophages in lymphoid tissues and colon, with enteric
neuronal ganglion cells in colon or with adipocytes in white fat. PrPSc localized
in macrophage phagolysosomes lacked discernable fibrils and might be undergoing
degradation. Furthermore, in contrast to wild-type mice expressing GPI-anchored
PrP, in lymphoid tissues of tg anchorless mice, PrPSc was not associated with
follicular dendritic cells (FDC), and FDC did not display typical
prion-associated pathogenic changes.
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