23 results on '"Våge J"'
Search Results
2. Association of dopamine- and serotonin-related genes with canine aggression
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Våge, J., Wade, C., Biagi, T., Fatjó, J., Amat, M., Lindblad-Toh, K., and Lingaas, F.
- Published
- 2010
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3. Differential gene expression in brain tissues of aggressive and non-aggressive dogs
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Tverdal Aage, Arnet Ellen, Bønsdorff Tina B, Våge Jørn, and Lingaas Frode
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Veterinary medicine ,SF600-1100 - Abstract
Abstract Background Canine behavioural problems, in particular aggression, are important reasons for euthanasia of otherwise healthy dogs. Aggressive behaviour in dogs also represents an animal welfare problem and a public threat. Elucidating the genetic background of adverse behaviour can provide valuable information to breeding programs and aid the development of drugs aimed at treating undesirable behaviour. With the intentions of identifying gene-specific expression in particular brain parts and comparing brains of aggressive and non-aggressive dogs, we studied amygdala, frontal cortex, hypothalamus and parietal cortex, as these tissues are reported to be involved in emotional reactions, including aggression. Based on quantitative real-time PCR (qRT-PCR) in 20 brains, obtained from 11 dogs euthanised because of aggressive behaviour and nine non-aggressive dogs, we studied expression of nine genes identified in an initial screening by subtraction hybridisation. Results This study describes differential expression of the UBE2V2 and ZNF227 genes in brains of aggressive and non-aggressive dogs. It also reports differential expression for eight of the studied genes across four different brain tissues (amygdala, frontal cortex, hypothalamus, and parietal cortex). Sex differences in transcription levels were detected for five of the nine studied genes. Conclusions The study showed significant differences in gene expression between brain compartments for most of the investigated genes. Increased expression of two genes was associated with the aggression phenotype. Although the UBE2V2 and ZNF227 genes have no known function in regulation of aggressive behaviour, this study contributes to preliminary data of differential gene expression in the canine brain and provides new information to be further explored.
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- 2010
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4. Single nucleotide polymorphisms (SNPs) in coding regions of canine dopamine- and serotonin-related genes
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Lingaas Frode and Våge Jørn
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Genetics ,QH426-470 - Abstract
Abstract Background Polymorphism in genes of regulating enzymes, transporters and receptors of the neurotransmitters of the central nervous system have been associated with altered behaviour, and single nucleotide polymorphisms (SNPs) represent the most frequent type of genetic variation. The serotonin and dopamine signalling systems have a central influence on different behavioural phenotypes, both of invertebrates and vertebrates, and this study was undertaken in order to explore genetic variation that may be associated with variation in behaviour. Results Single nucleotide polymorphisms in canine genes related to behaviour were identified by individually sequencing eight dogs (Canis familiaris) of different breeds. Eighteen genes from the dopamine and the serotonin systems were screened, revealing 34 SNPs distributed in 14 of the 18 selected genes. A total of 24,895 bp coding sequence was sequenced yielding an average frequency of one SNP per 732 bp (1/732). A total of 11 non-synonymous SNPs (nsSNPs), which may be involved in alteration of protein function, were detected. Of these 11 nsSNPs, six resulted in a substitution of amino acid residue with concomitant change in structural parameters. Conclusion We have identified a number of coding SNPs in behaviour-related genes, several of which change the amino acids of the proteins. Some of the canine SNPs exist in codons that are evolutionary conserved between five compared species, and predictions indicate that they may have a functional effect on the protein. The reported coding SNP frequency of the studied genes falls within the range of SNP frequencies reported earlier in the dog and other mammalian species. Novel SNPs are presented and the results show a significant genetic variation in expressed sequences in this group of genes. The results can contribute to an improved understanding of the genetics of behaviour.
- Published
- 2008
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5. Assessing freedom from chronic wasting disease in semi-domesticated reindeer in Norway and Sweden.
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Baron JN, Mysterud A, Hopp P, Rosendal T, Frössling J, Benestad SL, Våge J, Nöremark M, and Viljugrein H
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- Animals, Norway epidemiology, Sweden epidemiology, Prevalence, Reindeer, Wasting Disease, Chronic epidemiology
- Abstract
Establishing freedom from disease is a key component of surveillance and may have direct consequences for trade and economy. Transboundary populations pose challenges in terms of variable legislation, efforts, and data availability between countries, often limiting surveillance efficiency. Chronic wasting disease (CWD) is a contagious prion disease of cervids. The long incubation period and slow initial epidemic growth make it notoriously difficult to detect CWD in the early phase of an epidemic. The recent emergence of CWD in wild reindeer in Norway poses a threat to approximately 250,000 semi-domesticated reindeer in Norway and 250,000 in Sweden, including transboundary populations. Here, we provide a first analysis of surveillance data (2016-2022) from all reindeer districts in Norway and Sweden to determine the probability of freedom from CWD infection. During the six years, 6017 semi-domesticated reindeer were tested in Sweden and 51,974 in Norway. Most samples came from healthy slaughtered animals (low risk). Reindeer use large and remote areas and (high risk) samples from fallen stock and animals with clinical signs were difficult to obtain. A scenario tree model was run for seven different set of values for the input parameters (design prevalence within and between districts, probability of introduction, and relative risks) to determine the effect on surveillance sensitivity. At the national level, the mean probability of disease freedom was 59.0 % in Sweden and 87.0 % in Norway by 2021. The most marked effect on sensitivity was varying the design prevalence both within and between districts. Uncertainty about relative risk ratios affected sensitivity for Sweden more than for Norway, due to the higher proportion of animals in the high-risk group in the former (13.8 % vs. 2.1 %, respectively). A probability of disease freedom of 90 % or higher was reached in 8.2 % of the 49 districts in Sweden and 43.5 % of the 46 districts in Norway for a design prevalence of 0.5 %. The probability of freedom remained below 60 % in 29 districts (59.2 %) in Sweden and 10 districts (21.7 %) in Norway. At the national level, only Norway had a sufficiently large number of samples to reach a probability of more than 95 % of disease freedom within a period of 10 years. Our cross-border assessment forms an important knowledge base for designing future surveillance efforts depending on the spatial pattern of prevalence of CWD and risk of spread., Competing Interests: Declaration of Competing Interest We confirm that our work has not been submitted, published or accepted for publication, nor is being considered for publication elsewhere, either in whole or substantial part. The authors declare that there is no conflict of interest. All authors have seen and approved the manuscript being submitted., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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6. Classical BSE dismissed as the cause of CWD in Norwegian red deer despite strain similarities between both prion agents.
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Marín-Moreno A, Benestad SL, Barrio T, Pirisinu L, Espinosa JC, Tran L, Huor A, Di Bari MA, Eraña H, Maddison BC, D'Agostino C, Fernández-Borges N, Canoyra S, Jerez-Garrido N, Castilla J, Spiropoulos J, Bishop K, Gough KC, Nonno R, Våge J, Andréoletti O, and Torres JM
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- Animals, Norway, Blotting, Western veterinary, Enzyme-Linked Immunosorbent Assay veterinary, Prions metabolism, Cattle, Immunohistochemistry veterinary, PrPSc Proteins metabolism, Deer, Encephalopathy, Bovine Spongiform, Wasting Disease, Chronic
- Abstract
The first case of CWD in a Norwegian red deer was detected by a routine ELISA test and confirmed by western blotting and immunohistochemistry in the brain stem of the animal. Two different western blotting tests were conducted independently in two different laboratories, showing that the red deer glycoprofile was different from the Norwegian CWD reindeer and CWD moose and from North American CWD. The isolate showed nevertheless features similar to the classical BSE (BSE-C) strain. Furthermore, BSE-C could not be excluded based on the PrP
Sc immunohistochemistry staining in the brainstem and the absence of detectable PrPSc in the lymphoid tissues. Because of the known ability of BSE-C to cross species barriers as well as its zoonotic potential, the CWD red deer isolate was submitted to the EURL Strain Typing Expert Group (STEG) as a BSE-C suspect for further investigation. In addition, different strain typing in vivo and in vitro strategies aiming at identifying the BSE-C strain in the red deer isolate were performed independently in three research groups and BSE-C was not found in it. These results suggest that the Norwegian CWD red deer case was infected with a previously unknown CWD type and further investigation is needed to determine the characteristics of this potential new CWD strain., (© 2024. The Author(s).)- Published
- 2024
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7. Harvest and decimation affect genetic drift and the effective population size in wild reindeer.
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Kvalnes T, Flagstad Ø, Våge J, Strand O, Viljugrein H, and Sæther BE
- Abstract
Harvesting and culling are methods used to monitor and manage wildlife diseases. An important consequence of these practices is a change in the genetic dynamics of affected populations that may threaten their long-term viability. The effective population size ( N
e ) is a fundamental parameter for describing such changes as it determines the amount of genetic drift in a population. Here, we estimate Ne of a harvested wild reindeer population in Norway. Then we use simulations to investigate the genetic consequences of management efforts for handling a recent spread of chronic wasting disease, including increased adult male harvest and population decimation. The Ne / N ratio in this population was found to be 0.124 at the end of the study period, compared to 0.239 in the preceding 14 years period. The difference was caused by increased harvest rates with a high proportion of adult males (older than 2.5 years) being shot (15.2% in 2005-2018 and 44.8% in 2021). Increased harvest rates decreased Ne in the simulations, but less sex biased harvest strategies had a lower negative impact. For harvest strategies that yield stable population dynamics, shifting the harvest from calves to adult males and females increased Ne . Population decimation always resulted in decreased genetic variation in the population, with higher loss of heterozygosity and rare alleles with more severe decimation or longer periods of low population size. A very high proportion of males in the harvest had the most severe consequences for the loss of genetic variation. This study clearly shows how the effects of harvest strategies and changes in population size interact to determine the genetic drift of a managed population. The long-term genetic viability of wildlife populations subject to a disease will also depend on population impacts of the disease and how these interact with management actions., Competing Interests: The authors have no conflict of interest to declare., (© 2024 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)- Published
- 2024
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8. Sporadic cases of chronic wasting disease in old moose - an epidemiological study.
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Hopp P, Rolandsen CM, Korpenfelt SL, Våge J, Sörén K, Solberg EJ, Averhed G, Pusenius J, Rosendal T, Ericsson G, Bakka HC, Mysterud A, Gavier-Widén D, Hautaniemi M, Ågren E, Isomursu M, Madslien K, Benestad SL, and Nöremark M
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- Female, Male, Animals, Epidemiologic Studies, Brain, Cluster Analysis, Wasting Disease, Chronic, Deer
- Abstract
Transmissible spongiform encephalopathies or prion diseases comprise diseases with different levels of contagiousness under natural conditions. The hypothesis has been raised that the chronic wasting disease (CWD) cases detected in Nordic moose ( Alces alces ) may be less contagious, or not contagious between live animals under field conditions. This study aims to investigate the epidemiology of CWD cases detected in moose in Norway, Sweden and Finland using surveillance data from 2016 to 2022.In total, 18 CWD cases were detected in Nordic moose. All moose were positive for prion (PrP
res ) detection in the brain, but negative in lymph nodes, all were old (mean 16 years; range 12-20) and all except one, were female. Age appeared to be a strong risk factor, and the sex difference may be explained by few males reaching high age due to hunting targeting calves, yearlings and males.The cases were geographically scattered, distributed over 15 municipalities. However, three cases were detected in each of two areas, Selbu in Norway and Arjeplog-Arvidsjaur in Sweden. A Monte Carlo simulation approach was applied to investigate the likelihood of such clustering occurring by chance, given the assumption of a non-contagious disease. The empirical P -value for obtaining three cases in one Norwegian municipality was less than 0.05, indicating clustering. However, the moose in Selbu were affected by different CWD strains, and over a 6 year period with intensive surveillance, the apparent prevalence decreased, which would not be expected for an ongoing outbreak of CWD. Likewise, the three cases in Arjeplog-Arvidsjaur could also indicate clustering, but management practices promotes a larger proportion of old females and the detection of the first CWD case contributed to increased awareness and sampling.The results of our study show that the CWD cases detected so far in Nordic moose have a different epidemiology compared to CWD cases reported from North America and in Norwegian reindeer ( Rangifer tarandus tarandus ). The results support the hypothesis that these cases are less contagious or not contagious between live animals under field conditions. To enable differentiation from other types of CWD, we support the use of sporadic CWD (sCWD) among the names already in use.- Published
- 2024
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9. Heterogeneity of pathological prion protein accumulation in the brain of moose (Alces alces) from Norway, Sweden and Finland with chronic wasting disease.
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Sola D, Tran L, Våge J, Madslien K, Vuong TT, Korpenfelt SL, Ågren EO, Averhed G, Nöremark M, Sörén K, Isaksson M, Acín C, Badiola JJ, Gavier-Widén D, and Benestad SL
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- Animals, Prion Proteins, Finland epidemiology, Sweden epidemiology, Brain, Norway epidemiology, Wasting Disease, Chronic epidemiology, Reindeer, Prions, Deer
- Abstract
Prion diseases are a group of neurodegenerative, transmissible, and fatal disorders that affect several animal species. They are characterized by the conformational conversion of the cellular prion protein (PrP
C ) into the pathological prion protein (PrPSc ). In 2016, chronic wasting disease (CWD) gained great importance at European level due to the first disease detection in a wild reindeer (Rangifer tarandus) in Norway. The subsequent intensive CWD surveillance launched in cervids resulted in the detection of CWD in moose (Alces alces), with 11 cases in Norway, 3 in Finland and 4 in Sweden. These moose cases differ considerably from CWD cases in North American and reindeer in Norway, as PrPSc was detectable in the brain but not in lymphoid tissues. These facts suggest the occurrence of a new type of CWD. Here, we show some immunohistochemical features that are clearly different from CWD cases in North American and Norwegian reindeer. Further, the different types of PrPSc deposits found among moose demonstrate strong variations between the cases, supporting the postulation that these cases could carry multiple strains of CWD., (© 2023. L’Institut National de Recherche en Agriculture, Alimentation et Environnement (INRAE).)- Published
- 2023
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10. Are rapid tests and confirmatory western blot used for cattle and small ruminants TSEs reliable tools for the diagnosis of Chronic Wasting Disease in Europe?
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Mazza M, Tran L, Loprevite D, Cavarretta MC, Meloni D, Dell'Atti L, Våge J, Madslien K, Vuong TT, Bozzetta E, and Benestad SL
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- Animals, Cattle, Europe, Ruminants, Blotting, Western, Reindeer, Wasting Disease, Chronic diagnosis, Deer
- Abstract
The first case of CWD in Europe was detected in a Norwegian reindeer in 2016, followed later by two CWD cases in Norwegian moose. To prevent the potential spread of CWD to the EU, the European Commission (Regulation EU 2017_1972) implemented a CWD surveillance programme in cervids in the six countries having reindeer and or moose (Estonia, Finland, Latvia, Lithuania, Poland, and Sweden). Each country had to test a minimum of 3000 cervids for CWD using diagnostic rapid tests approved by the EC Regulation. Experimental transmission studies in rodents have demonstrated that the CWD strains found in Norwegian reindeer are different from those found in moose and that these European strains are all different from the North American ones. Data on the performances of authorised rapid tests are limited for CWD (from North America) and are currently minimal for CWD from Europe, due to the paucity of positive material. The aim of this study was to evaluate the diagnostic performances of three of the so-called "rapid" tests, commercially available and approved for TSE diagnosis in cattle and small ruminants, to detect the CWD strains circulating in Europe. The performances of these three tests were also compared to two different confirmatory western blot methods. Using parallel testing on the same panel of available samples, we evaluated here the analytical sensitivity of these methods for TSE diagnosis of CWD in Norwegian cervids tissues. Our results show that all the methods applied were able to detect the CWD positive samples even if differences in analytical sensitivity were clearly observed. Although this study could not assess the test accuracy, due to the small number of samples available, it is conceivable that the rapid and confirmatory diagnostic systems applied for CWD surveillance in Northern Europe are reliable tools., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Mazza et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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11. Humanized Transgenic Mice Are Resistant to Chronic Wasting Disease Prions From Norwegian Reindeer and Moose.
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Wadsworth JDF, Joiner S, Linehan JM, Jack K, Al-Doujaily H, Costa H, Ingold T, Taema M, Zhang F, Sandberg MK, Brandner S, Tran L, Vikøren T, Våge J, Madslien K, Ytrehus B, Benestad SL, Asante EA, and Collinge J
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- Animals, Humans, Mice, Mice, Transgenic, Norway, Deer metabolism, Prions genetics, Prions metabolism, Reindeer metabolism, Wasting Disease, Chronic genetics
- Abstract
Chronic wasting disease (CWD) is the transmissible spongiform encephalopathy or prion disease affecting cervids. In 2016, the first cases of CWD were reported in Europe in Norwegian wild reindeer and moose. The origin and zoonotic potential of these new prion isolates remain unknown. In this study to investigate zoonotic potential we inoculated brain tissue from CWD-infected Norwegian reindeer and moose into transgenic mice overexpressing human prion protein. After prolonged postinoculation survival periods no evidence for prion transmission was seen, suggesting that the zoonotic potential of these isolates is low., Competing Interests: Potential conflict of interests. J. C. is a director and J. C. and J. D. F. W. are shareholders of D-Gen, Ltd, an academic spin-out company working in the field of prion disease diagnosis, decontamination, and therapeutics. D-Gen supplied the ICSM 35 antibody used in this study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2022
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12. Chronic wasting disease in Norway-A survey of prion protein gene variation among cervids.
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Güere ME, Våge J, Tharaldsen H, Kvie KS, Bårdsen BJ, Benestad SL, Vikøren T, Madslien K, Rolandsen CM, Tranulis MA, and Røed KH
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- Animals, Norway epidemiology, Prion Proteins genetics, Deer genetics, Prions genetics, Reindeer genetics, Wasting Disease, Chronic epidemiology, Wasting Disease, Chronic genetics
- Abstract
Susceptibility of cervids to Chronic Wasting Disease (CWD), a prion disease, can be modulated by variations in the prion protein gene (PRNP), encoding the cellular prion protein (PrP
C ). In prion diseases, PrPC is conformationally converted to pathogenic conformers (PrPSc ), aggregates of which comprise infectious prions. CWD has recently been observed in its contagious form in Norwegian reindeer (Rangifer tarandus) and in novel, potentially sporadic forms, here called 'atypical CWD', in moose (Alces alces) and red deer (Cervus elaphus). To estimate relative susceptibility of different Norwegian cervid species to CWD, their non-synonymous PRNP variants were analyzed. In reindeer, seven PRNP alleles were observed and in red deer and moose two alleles were present, whereas roe deer (Capreolus capreolus) PRNP was monomorphic. One 'archetypal' PRNP allele associated with susceptibility was common to all four cervid species. The distribution of PRNP alleles differed between wild and semi-domesticated reindeer, with alleles associated with a high susceptibility occurring, on average, above 55% in wild reindeer and below 20% in semi-domesticated reindeer. This difference may reflect the diverse origins of the populations and/or selection processes during domestication and breeding. Overall, PRNP genetic data indicate considerable susceptibility to CWD among Norwegian cervids and suggest that PRNP homozygosity may be a risk factor for the atypical CWD observed in moose. The CWD isolates found in the Norwegian cervid species differ from those previously found in Canada and USA. Our study provides an overview of the PRNP genetics in populations exposed to these emerging strains that will provide a basis for understanding these strains' dynamics in relation to PRNP variability., (© 2021 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)- Published
- 2022
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13. Chronic wasting disease in Europe: new strains on the horizon.
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Tranulis MA, Gavier-Widén D, Våge J, Nöremark M, Korpenfelt SL, Hautaniemi M, Pirisinu L, Nonno R, and Benestad SL
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- Animals, Europe, Sheep, Deer, Prions genetics, Scrapie, Sheep Diseases, Wasting Disease, Chronic epidemiology
- Abstract
Prion diseases are fatal neurodegenerative disorders with known natural occurrence in humans and a few other mammalian species. The diseases are experimentally transmissible, and the agent is derived from the host-encoded cellular prion protein (PrP
C ), which is misfolded into a pathogenic conformer, designated PrPSc (scrapie). Aggregates of PrPSc molecules, constitute proteinaceous infectious particles, known as prions. Classical scrapie in sheep and goats and chronic wasting disease (CWD) in cervids are known to be infectious under natural conditions. In CWD, infected animals can shed prions via bodily excretions, allowing direct host-to-host transmission or indirectly via prion-contaminated environments. The robustness of prions means that transmission via the latter route can be highly successful and has meant that limiting the spread of CWD has proven difficult. In 2016, CWD was diagnosed for the first time in Europe, in reindeer (Rangifer tarandus) and European moose (Alces alces). Both were diagnosed in Norway, and, subsequently, more cases were detected in a semi-isolated wild reindeer population in the Nordfjella area, in which the first case was identified. This population was culled, and all reindeer (approximately 2400) were tested for CWD; 18 positive animals, in addition to the first diagnosed case, were found. After two years and around 25,900 negative tests from reindeer (about 6500 from wild and 19,400 from semi-domesticated) in Norway, a new case was diagnosed in a wild reindeer buck on Hardangervidda, south of the Nordfjella area, in 2020. Further cases of CWD were also identified in moose, with a total of eight in Norway, four in Sweden, and two cases in Finland. The mean age of these cases is 14.7 years, and the pathological features are different from North American CWD and from the Norwegian reindeer cases, resembling atypical prion diseases such as Nor98/atypical scrapie and H- and L-forms of BSE. In this review, these moose cases are referred to as atypical CWD. In addition, two cases were diagnosed in red deer (Cervus elaphus) in Norway. The emergence of CWD in Europe is a threat to European cervid populations, and, potentially, a food-safety challenge, calling for a swift, evidence-based response. Here, we review data on surveillance, epidemiology, and disease characteristics, including prion strain features of the newly identified European CWD agents., (© 2021. The Author(s).)- Published
- 2021
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14. Risk-based surveillance of chronic wasting disease in semi-domestic reindeer.
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Viljugrein H, Hopp P, Benestad SL, Våge J, and Mysterud A
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- Animals, Norway, Prion Proteins, Epidemiological Monitoring veterinary, Prions, Reindeer, Wasting Disease, Chronic diagnosis, Wasting Disease, Chronic epidemiology
- Abstract
Reindeer pastoralism is a widespread practise across Fennoscandia and Russia. An outbreak of chronic wasting disease (CWD) among wild reindeer (Rangifer tarandus) poses a severe threat to the semi-domestic reindeer herding culture. Establishing surveillance is therefore key, but current models for surveillance of CWD are designed for wild cervids and rely on samples obtained from recreational hunters. Targeting animal groups with a higher infection probability is often used for more efficient disease surveillance. CWD has a long incubation period of 2-3 years, and the animals show clinical signs in the later stages of the infection i.e. 1-4 months prior to death. The semi-domestic reindeer are free-ranging most of the year, but during slaughtering in late fall, herders stress the animals in penned areas. This allows removal of animals with deviant behaviour or physical appearance, and such removals are likely to include animals in the clinical stages of CWD if the population is infected. In Norway, the semi-domestic reindeer in Filefjell is adjacent to a previously CWD infected wild population. We developed a risk-based surveillance method for this semi-domestic setting to establish the probability of freedom from infection over time, or enable early disease detection and mitigation. The surveillance scheme with a scenario tree using three risk categories (sample category, demographic group, and deviations in behaviour or physical appearance) was more effective and less invasive as compared to the surveillance method developed for wild reindeer. We also simulated how variation in susceptibility, incubation period and time for onset of clinical signs (linked to variation in the prion protein gene, PRNP) would potentially affect surveillance. Surveillance for CWD was mandatory within EU-member states with reindeer (2018-2020). The diversity of management systems and epidemiological settings will require the development of a set of surveillance systems suitable for each different context. Our surveillance model is designed for a population with a high risk of CWD introduction requiring massive sampling, while at the same time aiming to limit adverse effects to the populations in areas of surveillance., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2021
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15. Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein.
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Bian J, Kim S, Kane SJ, Crowell J, Sun JL, Christiansen J, Saijo E, Moreno JA, DiLisio J, Burnett E, Pritzkow S, Gorski D, Soto C, Kreeger TJ, Balachandran A, Mitchell G, Miller MW, Nonno R, Vikøren T, Våge J, Madslien K, Tran L, Vuong TT, Benestad SL, and Telling GC
- Subjects
- Animals, Animals, Genetically Modified, Deer, Mice, North America, Norway, PrPSc Proteins genetics, Prion Proteins genetics, Wasting Disease, Chronic genetics, Wasting Disease, Chronic transmission
- Abstract
Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrPSc in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrPSc conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: CS is a Founder, Chief Scientific Officer and Member of the Board of Directors of Amprion Inc, a biotechnology company that focuses on the commercial use of PMCA and RT-QuIC for high-sensitivity detection of misfolded protein aggregates including prion diseases. The University of Texas Health Science Center at Houston has licensed patents and patent applications to Amprion. The remaining authors declare that they have no conflicts of interest with the contents of this article.
- Published
- 2021
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16. Distribution, prevalence and intensity of moose nose bot fly ( Cephenemyia ulrichii ) larvae in moose ( Alces alces ) from Norway.
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Rolandsen CM, Madslien K, Ytrehus B, Hamnes IS, Solberg EJ, Mysterud A, Vikøren T, Våge J, Hanssen O, and Miller AL
- Abstract
High host density combined with climate change may lead to invasion of harmful parasites in cervid (host) populations. Bot flies (Diptera: Oestridae) are a group of ectoparasites that may have strong impact on their hosts, but data on the current distribution, prevalence and intensity of the moose nose bot fly ( Cephenemyia ulrichii ) in Scandinavia are lacking. We estimated prevalence and intensity of nose bot fly larvae in 30 moose from southern and 79 moose from central Norway. All larvae detected were identified as the moose nose bot fly. We found surprisingly high prevalence in these areas, which are up to 1300 km south-southwest of the first published location in Norway and west of the distribution in Sweden. Prevalence (0.44-1.00) was higher in areas with higher moose density. Parasite intensity in hunter killed moose was higher in central Norway (mean 5.7) than southern Norway (mean 2.9), and in both regions higher in calves and yearlings than adults. Fallen moose had higher parasite intensity (mean 9.8) compared to hunter killed moose in the subsample from central Norway, suggesting a link to host condition or behavior. Our study provides evidence of parasite range expansion, and establishing monitoring appears urgent to better understand impact on host populations., Competing Interests: None., (© 2021 The Authors.)
- Published
- 2021
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17. First Detection of Chronic Wasting Disease in Moose (Alces alces) in Sweden.
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Ågren EO, Sörén K, Gavier-Widén D, Benestad SL, Tran L, Wall K, Averhed G, Doose N, Våge J, and Nöremark M
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- Animals, Female, Sweden epidemiology, Wasting Disease, Chronic epidemiology, Wasting Disease, Chronic pathology, Brain pathology, Deer, Wasting Disease, Chronic diagnosis
- Abstract
We report the first detection of chronic wasting disease (CWD) in Sweden, in three old female moose (Alces alces). Prions (PrPCWD) were detected in brain but not in lymph nodes. The findings are similar to previously described CWD cases in old moose in Norway, where a spontaneous origin is hypothesized., (© Wildlife Disease Association 2021.)
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- 2021
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18. Studies in bank voles reveal strain differences between chronic wasting disease prions from Norway and North America.
- Author
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Nonno R, Di Bari MA, Pirisinu L, D'Agostino C, Vanni I, Chiappini B, Marcon S, Riccardi G, Tran L, Vikøren T, Våge J, Madslien K, Mitchell G, Telling GC, Benestad SL, and Agrimi U
- Subjects
- Adaptation, Physiological, Animals, Brain pathology, Nerve Degeneration complications, Nerve Degeneration pathology, North America epidemiology, Norway epidemiology, Phenotype, Species Specificity, Wasting Disease, Chronic complications, Wasting Disease, Chronic transmission, Arvicolinae physiology, Prions metabolism, Wasting Disease, Chronic epidemiology
- Abstract
Chronic wasting disease (CWD) is a relentless epidemic disorder caused by infectious prions that threatens the survival of cervid populations and raises increasing public health concerns in North America. In Europe, CWD was detected for the first time in wild Norwegian reindeer ( Rangifer tarandus ) and moose ( Alces alces ) in 2016. In this study, we aimed at comparing the strain properties of CWD prions derived from different cervid species in Norway and North America. Using a classical strain typing approach involving transmission and adaptation to bank voles ( Myodes glareolus ), we found that prions causing CWD in Norway induced incubation times, neuropathology, regional deposition of misfolded prion protein aggregates in the brain, and size of their protease-resistant core, different from those that characterize North American CWD. These findings show that CWD prion strains affecting Norwegian cervids are distinct from those found in North America, implying that the highly contagious North American CWD prions are not the proximate cause of the newly discovered Norwegian CWD cases. In addition, Norwegian CWD isolates showed an unexpected strain variability, with reindeer and moose being caused by different CWD strains. Our findings shed light on the origin of emergent European CWD, have significant implications for understanding the nature and the ecology of CWD in Europe, and highlight the need to assess the zoonotic potential of the new CWD strains detected in Europe., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)
- Published
- 2020
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- View/download PDF
19. Chronic wasting disease associated with prion protein gene ( PRNP ) variation in Norwegian wild reindeer ( Rangifer tarandus ).
- Author
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Güere ME, Våge J, Tharaldsen H, Benestad SL, Vikøren T, Madslien K, Hopp P, Rolandsen CM, Røed KH, and Tranulis MA
- Subjects
- Animals, Cell Line, Tumor, Gene Frequency genetics, Genetic Association Studies, Genetic Predisposition to Disease, Geography, Humans, Norway, Open Reading Frames, Prion Proteins metabolism, Risk Factors, Genetic Variation, Prion Proteins genetics, Reindeer genetics, Wasting Disease, Chronic genetics
- Abstract
The emergence of CWD in Europe in 2016 and the first natural infection in wild reindeer warranted disease management. This led to the testing of 2424 hunted or culled reindeer during 2016-2018, from the infected subpopulation in the Nordfjella mountain range in Southern Norway. To identify any association between PRNP variation and CWD susceptibility, we characterized the open reading frame of the PRNP gene in 19 CWD positive reindeer and in 101 age category- and sex-matched CWD negative controls. Seven variant positions were identified: 6 single nucleotide variants (SNVs) and a 24 base pair (bp) deletion located between nucleotide position 238 and 272, encoding four instead of five octapeptide repeats. With a single exception, all variant positions but one were predicted to be non-synonymous. The synonymous SNV and the deletion are novel in reindeer. Various combinations of the non-synonymous variant positions resulted in the identification of five PRNP alleles (A-E) that structured into 14 genotypes. We identified an increased CWD risk in reindeer carrying two copies of the most common allele, A, coding for serine in position 225 (Ser225) and in those carrying allele A together with the 24 bp deletion.
- Published
- 2020
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20. Hunting strategies to increase detection of chronic wasting disease in cervids.
- Author
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Mysterud A, Hopp P, Alvseike KR, Benestad SL, Nilsen EB, Rolandsen CM, Strand O, Våge J, and Viljugrein H
- Subjects
- Age Factors, Animals, Computer Simulation, Female, Male, Models, Statistical, Population Dynamics, Sex Factors, Wasting Disease, Chronic prevention & control, Wasting Disease, Chronic transmission, Animal Culling methods, Animals, Wild, Conservation of Natural Resources methods, Epidemiological Monitoring veterinary, Reindeer, Wasting Disease, Chronic diagnosis
- Abstract
The successful mitigation of emerging wildlife diseases may involve controversial host culling. For livestock, 'preemptive host culling' is an accepted practice involving the removal of herds with known contact to infected populations. When applied to wildlife, this proactive approach comes in conflict with biodiversity conservation goals. Here, we present an alternative approach of 'proactive hunting surveillance' with the aim of early disease detection that simultaneously avoids undesirable population decline by targeting demographic groups with (1) a higher likelihood of being infected and (2) a lower reproductive value. We applied this harvesting principle to populations of reindeer to substantiate freedom of chronic wasting disease (CWD) infection. Proactive hunting surveillance reached 99% probability of freedom from infection (<4 reindeer infected) within 3-5 years, in comparison to ~10 years using ordinary harvest surveillance. However, implementation uncertainties linked to social issues appear challenging also with this kind of host culling.
- Published
- 2020
- Full Text
- View/download PDF
21. Mycoplasma conjunctivae- Associated Keratoconjunctivitis in Norwegian Muskox ( Ovibos moschatus ).
- Author
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Handeland K, Madslien K, Bretten T, Røtvei I, Våge J, and Tengs T
- Subjects
- Animals, Disease Outbreaks veterinary, Keratoconjunctivitis, Infectious epidemiology, Mycoplasma Infections epidemiology, Mycoplasma Infections microbiology, Norway epidemiology, Ruminants, Keratoconjunctivitis, Infectious microbiology, Mycoplasma Infections veterinary, Mycoplasma conjunctivae isolation & purification
- Abstract
In late summer 2014, an outbreak of ocular disease occurred in the Norwegian muskox ( Ovibos moschatus ) population. Animals showed rings of pus around their eyes and one euthanized animal was diagnosed with acute keratoconjunctivitis. The DNA sequence analysis of eye-swab samples from this animal revealed a high abundance of Mycoplasma conjunctivae .
- Published
- 2020
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- View/download PDF
22. First Detection of Chronic Wasting Disease in a Wild Red Deer ( Cervus elaphus ) in Europe.
- Author
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Vikøren T, Våge J, Madslien KI, Røed KH, Rolandsen CM, Tran L, Hopp P, Veiberg V, Heum M, Moldal T, Neves CGD, Handeland K, Ytrehus B, Kolbjørnsen Ø, Wisløff H, Terland R, Saure B, Dessen KM, Svendsen SG, Nordvik BS, and Benestad SL
- Subjects
- Animals, Brain pathology, Female, Norway epidemiology, Prions isolation & purification, Wasting Disease, Chronic pathology, Deer, Wasting Disease, Chronic epidemiology
- Abstract
Chronic wasting disease (CWD) is a fatal contagious prion disease naturally occurring in cervids in North America. In 2016, CWD was detected in wild reindeer ( Rangifer tarandus ) and moose ( Alces alces ) in Norway. Here, we report the first known naturally infected wild Norwegian red deer ( Cervus elaphus ).
- Published
- 2019
23. Novel Type of Chronic Wasting Disease Detected in Moose (Alces alces), Norway.
- Author
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Pirisinu L, Tran L, Chiappini B, Vanni I, Di Bari MA, Vaccari G, Vikøren T, Madslien KI, Våge J, Spraker T, Mitchell G, Balachandran A, Baron T, Casalone C, Rolandsen CM, Røed KH, Agrimi U, Nonno R, and Benestad SL
- Subjects
- Animals, Animals, Wild, Brain, Canada epidemiology, Europe, Female, Genotype, Immunohistochemistry, Norway, Prions genetics, Public Health Surveillance, Reindeer, Sheep, Wasting Disease, Chronic diagnosis, Wasting Disease, Chronic epidemiology
- Abstract
Chronic wasting disease (CWD) persists in cervid populations of North America and in 2016 was detected for the first time in Europe in a wild reindeer in Norway. We report the detection of CWD in 3 moose (Alces alces) in Norway, identified through a large scale surveillance program. The cases occurred in 13-14-year-old female moose, and we detected an abnormal form of prion protein (PrP
Sc ) in the brain but not in lymphoid tissues. Immunohistochemistry revealed that the moose shared the same neuropathologic phenotype, characterized by mostly intraneuronal deposition of PrPSc . This pattern differed from that observed in reindeer and has not been previously reported in CWD-infected cervids. Moreover, Western blot revealed a PrPSc type distinguishable from previous CWD cases and from known ruminant prion diseases in Europe, with the possible exception of sheep CH1641. These findings suggest that these cases in moose represent a novel type of CWD.- Published
- 2018
- Full Text
- View/download PDF
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