Transgenic minipig model of Huntington's disease exhibiting gradually progressing neurodegeneration

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F20%3A00115361" target="_blank" >RIV/00216224:14110/20:00115361 - isvavai.cz</a>

Result on the web

<a href="https://dmm.biologists.org/content/13/2/dmm041319.long" target="_blank" >https://dmm.biologists.org/content/13/2/dmm041319.long</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1242/dmm.041319" target="_blank" >10.1242/dmm.041319</a>

Result language

angličtina

Original language name

Transgenic minipig model of Huntington's disease exhibiting gradually progressing neurodegeneration

Original language description

Recently developed therapeutic approaches for the treatment of Huntington’s disease (HD) require preclinical testing in large animal models. The minipig is a suitable experimental animal because of its large gyrencephalic brain, body weight of 70-100 kg, long lifespan, and anatomical, physiological and metabolic resemblance to humans. The Libechov transgenic minipig model for HD (TgHD) has proven useful for proof of concept of developing new therapies. However, to evaluate the efficacy of different therapies on disease progression, a broader phenotypic characterization of the TgHD minipig is needed. In this study, we analyzed the brain tissues of TgHD minipigs at the age of 48 and 60-70 months, and compared them to wild-type animals. We were able to demonstrate not only an accumulation of different forms of mutant huntingtin (mHTT) in TgHD brain, but also pathological changes associated with cellular damage caused by mHTT. At 48 months, we detected pathological changes that included the demyelination of brain white matter, loss of function of striatal neurons in the putamen and activation of microglia. At 60-70 months, we found a clear marker of neurodegeneration: significant cell loss detected in the caudate nucleus, putamen and cortex. This was accompanied by clusters of structures accumulating in the neurites of some neurons, a sign of their degeneration that is also seen in Alzheimer’s disease, and a significant activation of astrocytes. In summary, our data demonstrate age-dependent neuropathology with later onset of neurodegeneration in TgHD minipigs.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Disease models & mechanisms

ISSN

1754-8403

e-ISSN

1754-8411

Volume of the periodical

13

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

1-12

UT code for WoS article

000518475500008

EID of the result in the Scopus database

2-s2.0-85076876205