Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F18%3A00495752" target="_blank" >RIV/67985904:_____/18:00495752 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/18:10390009

Result on the web

<a href="http://dx.doi.org/10.1159/000488592" target="_blank" >http://dx.doi.org/10.1159/000488592</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1159/000488592" target="_blank" >10.1159/000488592</a>

Result language

angličtina

Original language name

Gradual Phenotype Development in Huntington Disease Transgenic Minipig Model at 24 Months of Age

Original language description

Background: Huntington disease (HD) is an incurable neurodegenerative disease caused by the expansion of a polyglutamine sequence in a gene encoding the huntingtin (Htt) protein, which is expressed in almost all cells of the body. In addition to small animal models, new therapeutic approaches (including gene therapy) require large animal models as their large brains are a more realistic model for translational research. Objective: In this study, we describe phenotype development in transgenic minipigs (TgHD) expressing the N-terminal part of mutated human Htt at the age of 24 months. Methods: TgHD and wild-type littermates were compared. Western blot analysis and subcellular fractionation of different tissues was used to determine the fragmentation of Htt. Immunohistochemistry and optical analysis of coronal sections measuring aggregates, Htt expression, neuroinflammation, and myelination was applied. Furthermore, the expression of Golgi protein acyl-CoA binding domain containing 3 (ACBD3) was analyzed. Results: We found age-correlated Htt fragmentation in the brain. Among various tissues studied, the testes displayed the highest fragmentation, with Htt fragments detectable even in cell nuclei. Also, Golgi protein ACBD3 was upregulated in testes, which is in agreement with previously reported testicular degeneration in TgHD minipigs. Nevertheless, the TgHD-specific mutated Htt fragments were also present in the cytoplasm of striatum and cortex cells. Moreover, microglial cells were activated and myelination was slightly decreased, suggesting the development of a premanifest stage of neurodegeneration in TgHD minipigs. Conclusions: The gradual development of a neurodegenerative phenotype, accompanied with testicular degeneration, is observed in 24- month-old TgHD minipigs.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

<a href="/en/project/LO1609" target="_blank" >LO1609: Models of the Serious Human Diseases: Traumatic Spinal Cord Injury, Huntington’s Disease, Melanoma and Infertility</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neurodegenerative Diseases

ISSN

1660-2854

e-ISSN

—

Volume of the periodical

18

Issue of the periodical within the volume

2-3

Country of publishing house

CH - SWITZERLAND

Number of pages

13

Pages from-to

107-119

UT code for WoS article

000442610700007

EID of the result in the Scopus database

2-s2.0-85048172018