A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F18%3A00499872" target="_blank" >RIV/67985904:_____/18:00499872 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/18:10382063 RIV/00064165:_____/18:10382063
Result on the web
<a href="http://dx.doi.org/10.1242/dmm.035949" target="_blank" >http://dx.doi.org/10.1242/dmm.035949</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1242/dmm.035949" target="_blank" >10.1242/dmm.035949</a>
Alternative languages
Result language
angličtina
Original language name
A transgenic minipig model of Huntington's disease shows early signs of behavioral and molecular pathologies
Original language description
Huntington's disease (HD) is a monogenic, progressive, neurodegenerative disorder with currently no available treatment. The Libechov transgenic minipig model for HD (TgHD) displays neuroanatomical similarities to humans and exhibits slow disease progression, and is therefore more powerful than available mouse models for the development of therapy. The phenotypic characterization of this model is still ongoing, and it is essential to validate biomarkers to monitor disease progression and intervention. In this study, the behavioral phenotype (cognitive, motor and behavior) of the TgHD model was assessed, along with biomarkers for mitochondrial capacity, oxidative stress, DNA integrity and DNA repair at different ages (24, 36 and 48 months), and compared with age-matched controls. The TgHD minipigs showed progressive accumulation of the mutant huntingtin (mHTT) fragment in brain tissue and exhibited locomotor functional decline at 48 months. Interestingly, this neuropathology progressed without any significant age-dependent changes in any of the other biomarkers assessed. Rather, we observed genotype-specific effects on mitochondrial DNA (mtDNA) damage, mtDNA copy number, 8-oxoguanine DNA glycosylase activity and global level of the epigenetic marker 5-methylcytosine that we believe is indicative of a metabolic alteration that manifests in progressive neuropathology. Peripheral blood mononuclear cells (PBMCs) were relatively spared in the TgHD minipig, probably due to the lack of detectable mHTT. Our data demonstrate that neuropathology in the TgHD model has an age of onset of 48 months, and that oxidative damage and electron transport chain impairment represent later states of the disease that are not optimal for assessing interventions.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Disease Models & Mechanisms
ISSN
1754-8403
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
10
Country of publishing house
GB - UNITED KINGDOM
Number of pages
11
Pages from-to
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UT code for WoS article
000448830700010
EID of the result in the Scopus database
2-s2.0-85055595102