Immunologic and Molecular Biologic Studies of Prion Proteins in Bovine Spongiform Encephalopathy

Prusiner, Stanley B.; Füzi, M; Scott, Michael; Serban, Dan; Serban, Hana; Taraboulos, Albert; Gabriel, Jean Marc; Wells, G. A. H.; Wilesmith, J. W.; Bradley, R.; DeArmond, Stephen J.; Kristensson, Krister

doi:10.1093/infdis/167.3.602

Cited by 83 publications

(44 citation statements)

References 48 publications

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“…3,6,7,15,30,33,36,42,50,55,58,60,63,68,70 Based initially on spongiform changes and examination of large case numbers, the invariable predominance of lesions in the brainstem established this and, specifically, the medulla oblongata as the predilection brain region for diagnostic sampling. 18,30,53,63,66,68,70 Correlation of the highest concentrations of PrP Sc in the brainstem with the greatest degree of spongiform change 30,43,51,68 is considered suggestive of the initial brain pathologic alternations in BSE occurring in this region, consistent with the proposed pathogenesis of transmissible spongiform encephalopathy (TSE) in ruminants and laboratory rodent models after oral exposure. 4,5,13,20,26,29,39,40,61 This is supported by observations in a subset of clinical cases with restricted PrP Sc accumulation, which was invariably confined to the brainstem.…”

Section: Of Tissue Accumulations Of Prpmentioning

confidence: 77%

Experimental Classical Bovine Spongiform Encephalopathy

et al. 2010

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Tissues from sequential-kill time course studies of bovine spongiform encephalopathy (BSE) were examined to define PrP immunohistochemical labeling forms and map disease-specific labeling over the disease course after oral exposure to the BSE agent at two dose levels. Study was confined to brainstem, spinal cord, and certain peripheral nervous system ganglia-tissues implicated in pathogenesis and diagnosis or disease control strategies. Disease-specific labeling in the brainstem in 39 of 220 test animals showed the forms and patterns observed in natural disease and invariably preceded spongiform changes. A precise temporal pattern of increase in labeling was not apparent, but labeling was generally most widespread in clinical cases, and it always involved neuroanatomic locations in the medulla oblongata. In two cases, sparse labeling was confined to one or more neuroanatomic nuclei of the medulla oblongata. When involved, the spinal cord was affected at all levels, providing no indication of temporal spread within the cord axis or relative to the brainstem. Where minimal PrP labeling occurred in the thoracic spinal cord, it was consistent with initial involvement of general visceral efferent neurons. Labeling of ganglia involved only sensory ganglia and only when PrP was present in the brainstem and spinal cord. These experimental transmissions mimicked the neuropathologic findings in BSE-C field cases, independent of dose of agent or stage of disease. The model supports current diagnostic sampling approaches and control measures for the removal and destruction of nervous system tissues in slaughtered cattle.

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Section: Of Tissue Accumulations Of Prpmentioning

confidence: 77%

Experimental Classical Bovine Spongiform Encephalopathy

et al. 2010

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“…Experimental models of scrapie have demonstrated that PrP c plays a central role in the pathogenesis of prion disease (11). Generation of Prn-P º / º mice (12,13) has established the fact that PrP c is necessary for generating infectious particles as well as for developing neurodegenerative disease (12,14).…”

Section: Introductionmentioning

confidence: 99%

Disease-Associated Prion Protein Elicits Immunoglobulin M Responses In Vivo

Tayebi

Enever

Sattar

et al. 2004

Mol Med

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“…Transmission of prions by oral ingestion of infected tissues is well documented in rodents and more recently in cattle and sheep (6)(7)(8). The efficiency of transmission of prion disease between species is governed by a phenomenon commonly known as the ''species barrier.''…”

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confidence: 99%

Prions in skeletal muscle

Bosque

Ryou²,

Telling³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

142

107

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Here we report that mouse skeletal muscle can propagate prions and accumulate substantial titers of these pathogens. We found both high prion titers and the disease-causing isoform of the prion protein (PrP Sc ) in the skeletal muscle of wild-type mice inoculated with either the Me7 or Rocky Mountain Laboratory strain of murine prions. Particular muscles accumulated distinct levels of PrP Sc , with the highest levels observed in muscle from the hind limb. To determine whether prions are produced or merely accumulate intramuscularly, we established transgenic mice expressing either mouse or Syrian hamster PrP exclusively in muscle. Inoculating these mice intramuscularly with prions resulted in the formation of high titers of nascent prions in muscle. In contrast, inoculating mice in which PrP expression was targeted to hepatocytes resulted in low prion titers. Our data demonstrate that factors in addition to the amount of PrP expressed determine the tropism of prions for certain tissues. That some muscles are intrinsically capable of accumulating substantial titers of prions is of particular concern. Because significant dietary exposure to prions might occur through the consumption of meat, even if it is largely free of neural and lymphatic tissue, a comprehensive effort to map the distribution of prions in the muscle of infected livestock is needed. Furthermore, muscle may provide a readily biopsied tissue from which to diagnose prion disease in asymptomatic animals and even humans.

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Immunologic and Molecular Biologic Studies of Prion Proteins in Bovine Spongiform Encephalopathy

Cited by 83 publications

References 48 publications

Experimental Classical Bovine Spongiform Encephalopathy

Experimental Classical Bovine Spongiform Encephalopathy

Disease-Associated Prion Protein Elicits Immunoglobulin M Responses In Vivo

Prions in skeletal muscle

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