-
Je něco špatně v tomto záznamu ?
Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars
M. Macakova, B. Bohuslavova, P. Vochozkova, A. Pavlok, M. Sedlackova, D. Vidinska, K. Vochyanova, I. Liskova, I. Valekova, M. Baxa, Z. Ellederova, J. Klima, S. Juhas, J. Juhasova, J. Klouckova, M. Haluzik, J. Klempir, H. Hansikova, J. Spacilova,...
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26959244
DOI
10.1159/000443665
Knihovny.cz E-zdroje
- MeSH
- genetické vektory MeSH
- geneticky modifikovaná zvířata MeSH
- Huntingtonova nemoc metabolismus patologie MeSH
- Lentivirus genetika MeSH
- lidé MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- mutace * MeSH
- počet spermií MeSH
- prasata MeSH
- proliferace buněk fyziologie MeSH
- protein huntingtin genetika metabolismus MeSH
- spermie metabolismus patologie MeSH
- stárnutí metabolismus patologie MeSH
- testis metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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 F1 (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, immunohistochemistry 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.
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17000358
- 003
- CZ-PrNML
- 005
- 20200121105242.0
- 007
- ta
- 008
- 170103s2016 sz f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1159/000443665 $2 doi
- 024 7_
- $a 10.1159/000443665 $2 doi
- 035 __
- $a (PubMed)26959244
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a sz
- 100 1_
- $a Macakova, Monika $u Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov, Czech Republic.
- 245 10
- $a Mutated Huntingtin Causes Testicular Pathology in Transgenic Minipig Boars / $c M. Macakova, B. Bohuslavova, P. Vochozkova, A. Pavlok, M. Sedlackova, D. Vidinska, K. Vochyanova, I. Liskova, I. Valekova, M. Baxa, Z. Ellederova, J. Klima, S. Juhas, J. Juhasova, J. Klouckova, M. Haluzik, J. Klempir, H. Hansikova, J. Spacilova, R. Collins, I. Blumenthal, M. Talkowski, JF. Gusella, DS. Howland, M. DiFiglia, J. Motlik,
- 520 9_
- $a 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 F1 (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, immunohistochemistry 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.
- 650 _2
- $a stárnutí $x metabolismus $x patologie $7 D000375
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a geneticky modifikovaná zvířata $7 D030801
- 650 _2
- $a proliferace buněk $x fyziologie $7 D049109
- 650 _2
- $a modely nemocí na zvířatech $7 D004195
- 650 _2
- $a genetické vektory $7 D005822
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a protein huntingtin $x genetika $x metabolismus $7 D000071058
- 650 _2
- $a Huntingtonova nemoc $x metabolismus $x patologie $7 D006816
- 650 _2
- $a Lentivirus $x genetika $7 D016086
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 12
- $a mutace $7 D009154
- 650 _2
- $a počet spermií $7 D013076
- 650 _2
- $a spermie $x metabolismus $x patologie $7 D013094
- 650 _2
- $a prasata $7 D013552
- 650 _2
- $a miniaturní prasata $7 D013556
- 650 _2
- $a testis $x metabolismus $x patologie $7 D013737
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Bohuslavova, Bozena
- 700 1_
- $a Vochozkova, Petra
- 700 1_
- $a Pavlok, Antonin
- 700 1_
- $a Sedlackova, Miroslava
- 700 1_
- $a Vidinska, Daniela
- 700 1_
- $a Vochyanova, Klara
- 700 1_
- $a Liskova, Irena
- 700 1_
- $a Valekova, Ivona
- 700 1_
- $a Baxa, Monika
- 700 1_
- $a Ellederova, Zdenka
- 700 1_
- $a Klima, Jiri
- 700 1_
- $a Juhas, Stefan
- 700 1_
- $a Juhasova, Jana
- 700 1_
- $a Klouckova, Jana
- 700 1_
- $a Haluzik, Martin
- 700 1_
- $a Klempir, Jiri
- 700 1_
- $a Hansikova, Hana
- 700 1_
- $a Spacilova, Jana
- 700 1_
- $a Collins, Ryan
- 700 1_
- $a Blumenthal, Ian
- 700 1_
- $a Talkowski, Michael
- 700 1_
- $a Gusella, James F
- 700 1_
- $a Howland, David S
- 700 1_
- $a DiFiglia, Marian
- 700 1_
- $a Motlik, Jan
- 773 0_
- $w MED00180453 $t Neuro-degenerative diseases $x 1660-2862 $g Roč. 16, č. 3-4 (2016), s. 245-59
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/26959244 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20170103 $b ABA008
- 991 __
- $a 20200121105619 $b ABA008
- 999 __
- $a ok $b bmc $g 1179498 $s 960925
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2016 $b 16 $c 3-4 $d 245-59 $e 20160310 $i 1660-2862 $m Neuro-degenerative diseases $n Neurodegener Dis $x MED00180453
- LZP __
- $a Pubmed-20170103
