INT46273

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Context Info
Confidence 0.78
First Reported 1982
Last Reported 2010
Negated 3
Speculated 1
Reported most in Body
Documents 103
Total Number 147
Disease Relevance 110.34
Pain Relevance 9.25

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

Golgi apparatus (PRNP) endoplasmic reticulum (PRNP) nucleolus (PRNP)
plasma membrane (PRNP) nucleus (PRNP) cell cycle (PRNP)
Anatomy Link Frequency
brain 8
PRP 5
hippocampus 4
plaques 4
Head 3
PRNP (Homo sapiens)
PRNP - V210I (2) PRNP - P102L (1)
Pain Link Frequency Relevance Heat
iatrogenic 407 100.00 Very High Very High Very High
cerebral cortex 58 100.00 Very High Very High Very High
Serotonin 6 100.00 Very High Very High Very High
Demyelination 56 99.60 Very High Very High Very High
Spinal cord 139 99.52 Very High Very High Very High
Central nervous system 254 99.44 Very High Very High Very High
depression 12 99.36 Very High Very High Very High
medulla 153 99.20 Very High Very High Very High
anesthesia 171 99.02 Very High Very High Very High
headache 45 98.80 Very High Very High Very High
Disease Link Frequency Relevance Heat
Creutzfeldt Jakob Disease 5257 100.00 Very High Very High Very High
Disease 3114 100.00 Very High Very High Very High
Targeted Disruption 2767 100.00 Very High Very High Very High
Infection 1157 100.00 Very High Very High Very High
Alzheimer's Dementia 299 100.00 Very High Very High Very High
Sleep Disorders 179 100.00 Very High Very High Very High
Chronic Fatigue Syndrome 226 99.92 Very High Very High Very High
Gliosis 134 99.90 Very High Very High Very High
Syndrome 134 99.84 Very High Very High Very High
Kuru 1128 99.66 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The severity of neurotoxicity correlates with the level of Dpl expression [134] and can be rescued by PrPC expression [135], indicating that PrPC, Dpl and ?
Gene_expression (expression) of PrPC associated with drug induced neurotoxicity
1) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.42 Pain Relevance 0.06
Two types of genetic modification can be used to generate human PrP-expressing mice, either transgenic expression of human PrP on a mouse PrP knockout background [62] or direct replacement of mouse PrP with human PrP using gene knock-in technology [61].


Gene_expression (expression) of PrP associated with targeted disruption
2) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.43 Pain Relevance 0.03
Collectively, the existing data have yet to conclusively establish whether authentic high titre infectious prions have been generated de novo in mice expressing mouse PrP containing only human pathogenic mutations.
Gene_expression (expressing) of PrP
3) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.46 Pain Relevance 0.17
More recently, other human PrPC-expressing mouse models have been generated using knock-in technology which allows transgene integration at the normal genomic location and endogenous levels of expression under the control of normal gene regulatory elements [61,63,165–167].
Gene_expression (expressing) of PrPC associated with targeted disruption
4) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.99 Pain Relevance 0
This lack of susceptibility of Tg(HuPrP) mice, together with the earlier pioneering work of Scott et al. [162], subsequently led Telling and colleagues to generate mice that expressed a chimeric PrP protein in which a segment of mouse PrPC was replaced with the corresponding human PrP sequence [161].
Gene_expression (expressed) of PrP protein
5) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.13 Pain Relevance 0.04
Concomitant with this chimeric transgene approach, the endogenous mouse PrP allele was also removed by breeding Tg(HuPrP)152 mice to PrP null mice (Prnp°/°) to produce homozygous Tg(HuPrP)152/Prnp°/°[58,59].
Gene_expression (produce) of Prnp
6) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.07 Pain Relevance 0.04
Tg(GSSPrP)174 mice expressing high levels of mouse PrP 101L spontaneously develop neurological dysfunction at 166 days of age [196], however, PrPSc levels are low or undetectable, and brain extracts from affected mice do not transmit CNS degeneration to wild-type mice, but transmission to hamsters and Tg(GSSPrP)196 mice, expressing lower levels of the same mutant transgene product, was reported [204,205].
Gene_expression (expressing) of PrP in brain associated with anesthesia and central nervous system
7) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.51 Pain Relevance 0.22
Importantly, in this regard, transgenic mice expressing endogenous levels of mouse PrP 101L (generated by the gene knock-in approach) do not develop spontaneous neurodegeneration [165,192] while mice over-expressing wild-type PrPC have been found to develop spontaneous neurological dysfunction without generating infectious prions [116,206–208].
Gene_expression (expressing) of PrP associated with targeted disruption and anesthesia
8) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.52 Pain Relevance 0.20
Further, it is known that human PrPC functions less efficiently in mice than mouse PrPC, as over-expression is required to rescue a PrP null phenotype [168] and so ‘endogenous’ levels of heterologous PrPC expression may not in fact be the best model of susceptibility.


Gene_expression (expression) of PrPC
9) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.38 Pain Relevance 0
Early studies of human prions used primates [55–57]; however, following the demonstration in 1995 that the species barrier limiting transmission of human prions to wild-type mice can be obviated by expression of human PrP in the absence of endogenous mouse PrP [58,59] such ‘humanised’ transgenic mice have become key experimental models for studying human prion disease [43,60–65].
Gene_expression (expression) of PrP associated with targeted disruption and creutzfeldt jakob disease
10) Confidence 0.78 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.16 Pain Relevance 0.03
Very recently it has been revealed that axonal PrPC expression is required for peripheral myelin maintenance [154] and this finding correlates strongly with earlier demonstrations of extensive demyelination in transgenic mice expressing PrP with deletion mutants in the central domain [155–157].
Gene_expression (expression) of PrPC associated with targeted disruption and demyelination
11) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.08 Pain Relevance 0.08
The absence of a transmission barrier to sporadic CJD prions is not, however, uniformly observed in transgenic mice expressing human PrP 129 methionine on a Prnp null background.
Gene_expression (expressing) of PrP associated with targeted disruption and creutzfeldt jakob disease
12) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.07 Pain Relevance 0
Our research was the first to demonstrate transmission of BSE prions to transgenic mice expressing human PrP and these data confirmed that vCJD was caused by human exposure to the BSE prion strain [26,28] (Figure 3).
Gene_expression (expressing) of PrP associated with targeted disruption, creutzfeldt jakob disease and sprains and strains
13) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.87 Pain Relevance 0.04
Tg(HuPrP)110 and Tg(HuPrP)152 transgenic lines were made by co-expressing wild-type human PrP with valine at codon 129 in mice also expressing endogenous mouse PrPC[161].
Gene_expression (expressing) of PrP associated with targeted disruption
14) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.28 Pain Relevance 0.07
Very recently it has been revealed that axonal PrPC expression is required for peripheral myelin maintenance [154] and this finding correlates strongly with earlier demonstrations of extensive demyelination in transgenic mice expressing PrP with deletion mutants in the central domain [155–157].
Gene_expression (expressing) of PrP associated with targeted disruption and demyelination
15) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.09 Pain Relevance 0.08
Humanized transgenic mice expressing human PrP 129 valine on a Prnp null background are highly susceptible to sporadic CJD prions regardless of the PrPSc type or codon 129 genotype of the inoculum [25,26,58,59,122,164,169].
Gene_expression (expressing) of PrP associated with targeted disruption and creutzfeldt jakob disease
16) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.32 Pain Relevance 0
Although the chimeric transgene approach has provided extremely important advances to our understanding of human prion strain propagation [59,92,161,163,164], the demonstration that the human to mouse transmission barrier is overcome simply by expressing human PrPC in the absence of endogenous mouse PrPC[58,59] has established this as the most straightforward approach for investigating human prion strain diversity.
Gene_expression (expressing) of PrPC associated with sprains and strains
17) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.94 Pain Relevance 0.03
Importantly, in this regard, transgenic mice expressing endogenous levels of mouse PrP 101L (generated by the gene knock-in approach) do not develop spontaneous neurodegeneration [165,192] while mice over-expressing wild-type PrPC have been found to develop spontaneous neurological dysfunction without generating infectious prions [116,206–208].
Gene_expression (expressing) of PrPC associated with targeted disruption and anesthesia
18) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 0.45 Pain Relevance 0.20
Tg(HuPrP)110 and Tg(HuPrP)152 transgenic lines were made by co-expressing wild-type human PrP with valine at codon 129 in mice also expressing endogenous mouse PrPC[161].
Gene_expression (expressing) of PrPC associated with targeted disruption
19) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.37 Pain Relevance 0.07
Recently, Lindquist and colleagues have reported that mice expressing mouse PrP with L108M, V111M and D177N substitutions generated by knock-in technology spontaneously produce transmissible prions [202].


Gene_expression (expressing) of PrP associated with targeted disruption
20) Confidence 0.68 Published 2010 Journal Neuropathology and Applied Neurobiology Section Body Doc Link PMC3017745 Disease Relevance 1.20 Pain Relevance 0

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