Identification and futuristic role of novel polymorphism of caprine PrP gene

Given the critical role of the prion protein (PrP) in the transmission and pathogenesis of experimental scrapie, we investigated the PrP gene and its protein products in three hamster species, Chinese (CHa), Armenian (AHa), and Syrian (SHa), each of which were found to have distinctive scrapie incubation times. Passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with clinical signs of scrapie revealed characteristic patterns of neuropathology. Northern (RNA) analysis showed the size of PrP mRNA from CHa, AHa, and SHa hamsters to be 2.5, 2.4, and 2.1 kilobases, respectively. Immunoblotting demonstrated that the PrP isoforms were of similar size (33 to 35 kilodaltons); however, the monoclonal antibody 13A5 raised against SHa PrP did not react with the CHa or AHa PrP molecules. Comparison of the three predicted amino acid sequences revealed that each is distinct. Furthermore, differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans. Single polymorphisms in this region correlate with the presence or absence of amyloid plaques for a given hamster species or mouse inbred strain. Our findings demonstrate distinctive molecular, pathological, and clinical characteristics of scrapie in three related species and are consistent with the hypothesis that molecular properties of the host PrP play a pivotal role in determining the incubation time and neuropathological features of scrapie.

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Three hamster species with different scrapie incubation times and neuropathological features encode distinct prion proteins.

Molecular and Cellular Biology ◽

10.1128/mcb.10.3.1153 ◽

1990 ◽

Vol 10 (3) ◽

pp. 1153-1163 ◽

Cited By ~ 57

Author(s):

D H Lowenstein ◽

D A Butler ◽

D Westaway ◽

M P McKinley ◽

S J DeArmond ◽

...

Keyword(s):

Incubation Time ◽

Prion Proteins ◽

Inbred Mice ◽

Critical Role ◽

Clinical Signs ◽

Amino Acid Sequences ◽

Reading Frame ◽

Rna Analysis ◽

Prp Gene

Given the critical role of the prion protein (PrP) in the transmission and pathogenesis of experimental scrapie, we investigated the PrP gene and its protein products in three hamster species, Chinese (CHa), Armenian (AHa), and Syrian (SHa), each of which were found to have distinctive scrapie incubation times. Passaging studies demonstrated that the host species, and not the source of scrapie prions, determined the incubation time for each species, and histochemical studies of hamsters with clinical signs of scrapie revealed characteristic patterns of neuropathology. Northern (RNA) analysis showed the size of PrP mRNA from CHa, AHa, and SHa hamsters to be 2.5, 2.4, and 2.1 kilobases, respectively. Immunoblotting demonstrated that the PrP isoforms were of similar size (33 to 35 kilodaltons); however, the monoclonal antibody 13A5 raised against SHa PrP did not react with the CHa or AHa PrP molecules. Comparison of the three predicted amino acid sequences revealed that each is distinct. Furthermore, differences within the PrP open reading frame that uniquely distinguish the three hamster species are within a hydrophilic segment of 11 amino acids that includes polymorphisms linked to scrapie incubation times in inbred mice and an inherited prion disease of humans. Single polymorphisms in this region correlate with the presence or absence of amyloid plaques for a given hamster species or mouse inbred strain. Our findings demonstrate distinctive molecular, pathological, and clinical characteristics of scrapie in three related species and are consistent with the hypothesis that molecular properties of the host PrP play a pivotal role in determining the incubation time and neuropathological features of scrapie.

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Expression of doppel in the CNS of mice does not modulate transmissible spongiform encephalopathy disease

Journal of General Virology ◽

10.1099/0022-1317-83-3-705 ◽

2002 ◽

Vol 83 (3) ◽

pp. 705-711 ◽

Cited By ~ 35

Author(s):

Nadia L. Tuzi ◽

Elaine Gall ◽

David Melton ◽

Jean C. Manson

Keyword(s):

Late Onset ◽

Transmissible Spongiform Encephalopathy ◽

Structural Similarity ◽

Transmissible Spongiform Encephalopathies ◽

Spongiform Encephalopathy ◽

Spongiform Encephalopathies ◽

Naturally Occurring ◽

Prp Gene ◽

Apparent Influence

Late onset ataxia reported in three independently derived PrP null lines of mice has been attributed to the overexpression of the doppel protein in the CNS of these mice rather than to the loss of PrP. The central role of PrP in the transmissible spongiform encephalopathies (TSEs), the proximity of the gene which encodes doppel (Prnd) to the PrP gene (Prnp) and the structural similarity shared by PrP and doppel have led to the proposition that ataxia which develops during TSE disease could, in part, be due to doppel. In order to address this hypothesis, we have crossed our two inbred lines of PrP null mice, which either express (RCM) or do not express (NPU) the Prnd gene in the CNS, with mice expressing two Prnp a[108F189V] alleles of the PrP gene. We have found that the TSE infection does not influence the level of expression of Prnd in the CNS at the terminal stages of disease. Moreover, we have demonstrated that the level of expression of Prnd in the CNS has no influence on the incubation period, vacuolar pathology nor amount or distribution of PrPSc deposition in the brains of the TSE-infected mice. Doppel has therefore no apparent influence on the outcome of TSE disease in transgenic mice, suggesting it is unlikely to be involved in the naturally occurring TSE diseases in other species.

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Molecular genetics of human prion diseases

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.1994.0031 ◽

1994 ◽

Vol 343 (1306) ◽

pp. 371-378 ◽

Cited By ~ 19

Keyword(s):

Prion Disease ◽

Protein Gene ◽

Prion Diseases ◽

Strong Support ◽

Pituitary Hormones ◽

Prion Protein Gene ◽

Phenotypic Spectrum ◽

Prp Gene ◽

Codon 129

Human prion diseases occur in inherited, sporadic and acquired forms. The inherited forms are associated with coding mutations in the prion protein gene and the identification of one of these pathogenic mutations allows definitive diagnosis and has resulted in a widening of the previously recognized phenotypic spectrum of these diseases. Study of acquired prion disease provides evidence for genetic susceptibility to development of disease following treatment with contaminated pituitary hormones. Sporadic prion disease occurs predominately in individuals homozygous with respect to a common PrP polymorphism at residue 129. The identification of pathogenic PrP alleles and the role of the codon 129 PrP gene polymorphism in determining susceptibility to prion disease provides strong support for the idea that an abnormal isoform of PrP, PrP Sc , is the principal constituent of the prion and that its propagation involves direct PrP-PrP interactions which occur most readily between identical PrP molecules.

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Role of dactinomycin in the improved survival of children with Wilms' tumor

JAMA ◽

10.1001/jama.195.12.1005 ◽

1966 ◽

Vol 195 (12) ◽

pp. 1005-1009 ◽

Cited By ~ 18

Author(s):

D. J. Fernbach

Keyword(s):

Wilms Tumor

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Role of the allergist in diagnosis and management of patients with uveitis

JAMA ◽

10.1001/jama.195.3.167 ◽

1966 ◽

Vol 195 (3) ◽

pp. 167-172 ◽

Cited By ~ 2

Author(s):

T. E. Van Metre

Keyword(s):

Diagnosis And Management

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The power of norms to sway fused group members

Behavioral and Brain Sciences ◽

10.1017/s0140525x18001644 ◽

2018 ◽

Vol 41 ◽

Cited By ~ 1

Author(s):

Winnifred R. Louis ◽

Craig McGarty ◽

Emma F. Thomas ◽

Catherine E. Amiot ◽

Fathali M. Moghaddam

Keyword(s):

Evolutionary Anthropology ◽

Normative Systems ◽

Violent Extremism ◽

Identity Fusion ◽

Group Members

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.

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Elaborating the role of reflection and individual differences in the study of folk-economic beliefs

Behavioral and Brain Sciences ◽

10.1017/s0140525x18000274 ◽

2018 ◽

Vol 41 ◽

Author(s):

Kevin Arceneaux

Keyword(s):

Decision Making ◽

Individual Differences ◽

Cognitive Processes ◽

Evolutionary History ◽

Behavioral Responses ◽

History Of ◽

Economic Beliefs

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.

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The role of affect in feelings of obligation

Behavioral and Brain Sciences ◽

10.1017/s0140525x19002449 ◽

2020 ◽

Vol 43 ◽

Author(s):

Stefen Beeler-Duden ◽

Meltem Yucel ◽

Amrisha Vaish

Keyword(s):

Positive Emotions ◽

The Creation ◽

Sense Of Obligation

Abstract Tomasello offers a compelling account of the emergence of humans’ sense of obligation. We suggest that more needs to be said about the role of affect in the creation of obligations. We also argue that positive emotions such as gratitude evolved to encourage individuals to fulfill cooperative obligations without the negative quality that Tomasello proposes is inherent in obligations.

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