Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985904%3A_____%2F16%3A00459932" target="_blank" >RIV/67985904:_____/16:00459932 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14110/16:00089942 RIV/00216208:11110/16:10324318 RIV/00216208:11310/16:10324318 RIV/00023761:_____/16:N0000014 RIV/00064165:_____/16:10324318
Result on the web
<a href="http://dx.doi.org/10.1159/000443665" target="_blank" >http://dx.doi.org/10.1159/000443665</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1159/000443665" target="_blank" >10.1159/000443665</a>
Alternative languages
Result language
angličtina
Original language name
Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars
Original language description
Background: Huntington's disease is induced by CAG expansion in a single gene coding the huntingtin protein. The mutated huntingtin (mtHtt) primarily causes degeneration of neurons in the brain, but it also affects peripheral tissues, including testes. Objective: We studied sperm and testes of transgenic boars expressing the N-terminal region of human mtHtt. Methods: In this study, measures of reproductive parameters and electron microscopy (EM) images of spermatozoa and testes of transgenic (TgHD) and wild-type (WT) boars of Fl (24-48 months old) and F2 (12-36 months old) generations were compared. In addition, immunofluorescence, immunohistochemistry, Western blot, hormonal analysis and whole-genome sequencing were done in order to elucidate the effects of mtHtt. Results: Evidence for fertility failure of both TgHD generations was observed at the age of 13 months. Reproductive parameters declined and progressively worsened with age. EM revealed numerous pathological features in sperm tails and in testicular epithelium from 24- and 36-month-old TgHD boars. Moreover, innmunohistochemistry confirmed significantly lower proliferation activity of spermatogonia in transgenic testes. mtHtt was highly expressed in spermatozoa and testes of TgHD boars and localized in all cells of seminiferous tubules. Levels of fertility-related hormones did not differ in TgHD and WT siblings. Genome analysis confirmed that insertion of the lentiviral construct did not interrupt any coding sequence in the pig genome. Conclusions: The sperm and testicular degeneration of TgHD boars is caused by gain-of-function of the highly expressed mtHtt.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
FH - Neurology, neuro-surgery, nuero-sciences
OECD FORD branch
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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)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurodegenerative Diseases
ISSN
1660-2854
e-ISSN
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Volume of the periodical
16
Issue of the periodical within the volume
3-4
Country of publishing house
CH - SWITZERLAND
Number of pages
15
Pages from-to
245-259
UT code for WoS article
000374512500015
EID of the result in the Scopus database
2-s2.0-84961212403