0391811 20240903203026.620140310235959.9 10.3233/JHD-130001 22 s. P cav_un_epca*03977231879-639721 (2013)47-68IOS Press Huntington´s disease mutant huntingtin minipigs large animal model cav_un_auth*0265484 Baxa Monika Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0242508 Hruška-Plocháň Marian Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0245210 Juhás Štefan Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0105655 Vodička Petr Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0105623 Pavlok Antonín Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0264654 Juhásová Jana Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0246498 Miyanohara A. US cav_un_auth*0246496 Nejime T. US cav_un_auth*0105591 Klíma Jiří Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0290686 Mačáková Monika Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. cav_un_auth*0246497 Marsala S. US cav_un_auth*0290687 Weiss A. CH cav_un_auth*0016703 Kubíčková S. CZ cav_un_auth*0016704 Musilová P. CZ cav_un_auth*0277180 Vrtel R. CZ cav_un_auth*0290688 Sontag E. M. US cav_un_auth*0240180 Thompson L.M. US cav_un_auth*0101190 Schier Jan Zpracování obrazové informace Department of Image Processing ZOI ZOI UTIA-B Department of Image Processing Ústav teorie informace a automatizace AV ČR, v. v. i. cav_un_auth*0018382 Hansíková H. CZ cav_un_auth*0290689 Howland D. S. US cav_un_auth*0246500 Cattaneo E. IT cav_un_auth*0290690 DiFiglia M. US cav_un_auth*0265483 Marsala M. US cav_un_auth*0105617 Motlík Jan Laboratoř buněčné regenerace a plasticity Laboratory of Cell Regeneration and Plasticity LBRP UZFG-Y Biomedical Research Team Ústav živočišné fyziologie a genetiky AV ČR, v. v. i. TA01011466 GA TA ČR cav_un_auth*0272425 ED2.1.00/03.0124 GA MŠk cav_un_auth*0281636 Background: Some promising treatments for Huntington's disease (HD) may require pre-clinical testing in large animals. Minipig is a suitable species because of its large gyrencephalic brain and long lifespan. Objective: To generate HD transgenic (TgHD) minipigs encoding huntingtin (HTT)1–548 under the control of human HTT promoter. Methods: Transgenesis was achieved by lentiviral infection of porcine embryos. PCR assessment of gene transfer, observations of behavior, and postmortem biochemical and immunohistochemical studies were conducted. Results: One copy of the human HTT transgene encoding 124 glutamines integrated into chromosome 1 q24-q25 and successful germ line transmission occurred through successive generations (F0, F1, F2 and F3 generations). No developmental or gross motor deficits were noted up to 40 months of age. Mutant HTT mRNA and protein fragment were detected in brain and peripheral tissues. No aggregate formation in brain up to 16 months was seen by AGERA and filter retardation or by immunostaining. DARPP32 labeling in WT and TgHD minipig neostriatum was patchy. Analysis of 16 month old sibling pairs showed reduced intensity of DARPP32 immunoreactivity in neostriatal TgHD neurons compared to those of WT. Compared to WT, TgHD boars by one year had reduced fertility and fewer spermatozoa per ejaculate. In vitro analysis revealed a significant decline in the number of WT minipig oocytes penetrated by TgHD spermatozoa. Conclusions: The findings demonstrate successful establishment of a transgenic model of HD in minipig that should be valuable for testing long term safety of HD therapeutics. The emergence of HD-like phenotypes in the TgHD minipigs will require more study. 2014 EB 4 A 4a 20231122135608.9 RVO:67985904 RVO:67985556 http://hdl.handle.net/11104/0225353 S 2013 Soubory v repozitáři: A transgenic Minipig Model of Huntingtons Disease.pdf cav_un_epca*0397723 Journal of Huntington´s Disease 1879-6397 1879-6400 Roč. 2 č. 1 2013 47 68 IOS Press