Following the phenotype development of TgHD minipigs by invasive and noninvasive approach
Ellederová, Zdeňka; Baxa, Monika; Vidinská, Daniela; Bohuslavová, Božena; Vochozková, Petra; Šmatlíková, Petra; Klíma, Jiří; Valeková, Ivona; Ardan, Taras; Juhás, Štefan; Juhásová, Jana; Konvalinková, R.; Klempíř, J.; Pokorný, M.; Krupička, R.; Kauler, J.; Hansíková, H.; Motlík, Jan
2017 - anglický Recent promising treatments for Huntington’s disease (HD) may require pre-clinical testing in large animals. In 2009, we generated HD transgenic (TgHD) minipigs with one copy encoding the N-terminal part (548 aa) of human huntingtin (HTT) with 124 CAG/CAA repeats integrated into chromosome 1 q24-q25. The successful germ line transmission occurred through four successive generations. Klíčová slova: minipigs; Huntington´s disease Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Following the phenotype development of TgHD minipigs by invasive and noninvasive approach

Recent promising treatments for Huntington’s disease (HD) may require pre-clinical testing in large animals. In 2009, we generated HD transgenic (TgHD) minipigs with one copy encoding the N-terminal ...

Ellederová, Zdeňka; Baxa, Monika; Vidinská, Daniela; Bohuslavová, Božena; Vochozková, Petra; Šmatlíková, Petra; Klíma, Jiří; Valeková, Ivona; Ardan, Taras; Juhás, Štefan; Juhásová, Jana; Konvalinková, R.; Klempíř, J.; Pokorný, M.; Krupička, R.; Kauler, J.; Hansíková, H.; Motlík, Jan
Ústav živočišné fyziologie a genetiky, 2017

Evaluation of strategies for humanization of the entire porcine HTT locus
Vochozková, Petra; Klymiuk, N.; Wolf, E.; Ellederová, Zdeňka; Motlík, Jan
2017 - anglický Because fully suitable large animal models are still lacking for Huntington´s disease, we would like to generate a new minipig model which will have an entirely humanized HTT locus. Given the large size of the HTT gene (approx. 160 kb) we will test two different approaches to humanize the porcine HTT locus in porcine kidney cells (PKCs). Klíčová slova: minipig model; HTT locus Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Evaluation of strategies for humanization of the entire porcine HTT locus

Because fully suitable large animal models are still lacking for Huntington´s disease, we would like to generate a new minipig model which will have an entirely humanized HTT locus. Given the large ...

Vochozková, Petra; Klymiuk, N.; Wolf, E.; Ellederová, Zdeňka; Motlík, Jan
Ústav živočišné fyziologie a genetiky, 2017

Stimulating autophagy and reducing inclusions in mouse model of Huntington's disease via expression of transcription factor EB (TFEB)
Vodička, Petr; Chase, K.; Iulliano, M.; Tousley, A.; Valentine, D. T.; Sapp, E.; Kegel-Gleason, K. B.; Sena-Esteves, M.; Aronin, N.; DiFiglia, M.
2017 - anglický Mutant huntingtin (mHTT) is encoded by the Huntington’s disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the autophagosome-lysosomal pathway may have therapeutic benefit. Transcription factor EB (TFEB) regulates lysosome biogenesis and autophagy. We introduced cDNA encoding TFEB with an HA tag (TFEB-HA) under the control of neuron specific synapsin 1 promoter into the striatum of 3 month old HDQ175/Q7 mice using adeno-associated virus AAV2/9. Klíčová slova: mutant huntingtin Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Stimulating autophagy and reducing inclusions in mouse model of Huntington's disease via expression of transcription factor EB (TFEB)

Mutant huntingtin (mHTT) is encoded by the Huntington’s disease (HD) gene and its accumulation in the brain contributes to HD pathogenesis. Reducing mHTT levels through activation of the ...

Vodička, Petr; Chase, K.; Iulliano, M.; Tousley, A.; Valentine, D. T.; Sapp, E.; Kegel-Gleason, K. B.; Sena-Esteves, M.; Aronin, N.; DiFiglia, M.
Ústav živočišné fyziologie a genetiky, 2017

Body fluid exosomes as potential carriers of Huntington’s disease biomarkers
Kupcová Skalníková, Helena; Červenka, Jakub; Bohuslavová, Božena; Turnovcová, Karolína; Vodička, Petr
2017 - anglický Huntington’s disease (HD) is a hereditary neurodegenerative disorder characterized by a progressive motor, behavioural, and cognitive decline, ending in death. The cause of HD is an abnormal expansion of CAG repeats in HTT gene resulting in prolonged polyglutamine (polyQ) sequence in huntingtin protein (HTT). Huntingtin is a large protein (348 kDa) expressed ubiquitously through the body, with highest expression in the brain and testes. To study HD pathophysiology and to test experimental therapies, a transgenic HD minipig (TgHD) model expressing N-terminal part (N548-124Q) of human mutated huntingtin (mHTT) under the control of human huntingtin promoter was created in Libechov. Beside the mild neurological impairment, the TgHD boars show decreased fertility after 13th month of age. Klíčová slova: Huntington´s disease Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Body fluid exosomes as potential carriers of Huntington’s disease biomarkers

Huntington’s disease (HD) is a hereditary neurodegenerative disorder characterized by a progressive motor, behavioural, and cognitive decline, ending in death. The cause of HD is an abnormal expansion ...

Kupcová Skalníková, Helena; Červenka, Jakub; Bohuslavová, Božena; Turnovcová, Karolína; Vodička, Petr
Ústav živočišné fyziologie a genetiky, 2017

The effect of WNT5A and WNT7A on cartilage formation and anterior-posterior patterning of the limb
Killinger, Michael; Buchtová, Marcela
2017 - anglický Growth and patterning of the vertebrate limb is controlled by signals produced in the appical ectodermal ridge (AER) and by the zone of polarizing aktivity (ZPA). limb development requires tight interactions between these signalling centers to keep asymmetrical arrangement of all skeletal elements and their growth. Klíčová slova: limb Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. The effect of WNT5A and WNT7A on cartilage formation and anterior-posterior patterning of the limb

Growth and patterning of the vertebrate limb is controlled by signals produced in the appical ectodermal ridge (AER) and by the zone of polarizing aktivity (ZPA). limb development requires tight ...

Killinger, Michael; Buchtová, Marcela
Ústav živočišné fyziologie a genetiky, 2017

Potent anti-spasticity and anti-nociceptive effect of subpial GAD65 and VGAT gene delivery in rat and mice
Maršala, M.; Tadokoro, T.; Hernandez, M. B.; Navarro, M.; Maršala, S.; Miyanohara, A.; Juhás, Štefan; Juhásová, Jana; Platoshyn, O.
2017 - anglický In previous studies we have developed a novel spinal subpial (SP) AAV delivery technique in adult mice, rats and minipigs. Using this technique we have demonstrated potent and wide-spread transgene (GFP) expression in spinal white and gray matter after a single SP bolus of AAV9-UBI-GFP. Klíčová slova: rat; mouse Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Potent anti-spasticity and anti-nociceptive effect of subpial GAD65 and VGAT gene delivery in rat and mice

In previous studies we have developed a novel spinal subpial (SP) AAV delivery technique in adult mice, rats and minipigs. Using this technique we have demonstrated potent and wide-spread transgene ...

Maršala, M.; Tadokoro, T.; Hernandez, M. B.; Navarro, M.; Maršala, S.; Miyanohara, A.; Juhás, Štefan; Juhásová, Jana; Platoshyn, O.
Ústav živočišné fyziologie a genetiky, 2017

Evaluation of efficacy and bio-distribution of AAV5-miHTT in HD minipig brain
Bohuslavová, Božena; Juhás, Štefan; Juhásová, Jana; Ellederová, Zdeňka; Motlík, Jan
2016 - anglický Healthy minipigs (n=29) were pre-screened for serum AAV5 neutralizing antibodies (NABs) in serum by uniQure. Conclusions: Intrastriatal/intrathalamic bilateral application of AAV5-CAG-miHtt(3e13/1e13gctotal) or PBS/Sucrose (54μl/216μl) similarly to AA5-CAG-GFP didn´t cause any neurological deficit in transgenic as well as wild type animals. The body weight increased in all animals 84 days after AAV5-CAG-miHtt/PBS-Sucroseintrastriatal/intrathalamic delivery with two exceptions TGanimal L616 (AAV5-CAG-miHtt1e 13g ctotal) and WTanimal L485 (AAV5-CAG-miHtt3e13gc total). The TG boar N176 from group VII (PBS/Sucrose) died during narcosis 56 days after IP/IT application), shortly after CSF and blood collection.The boar breathed heavily and intermittently, then the heart stopped beat and resuscitation failed. We immediately flushed them by 20 L of PBS with heparin and collect all tissues. All animals had normal food consumption. Inflammatory proces in AAV5-CAG-miHtt (1e13 gc total) seems to be similar to PBS/Sucrose injected animals accompanied with no detectable histological pathologies. Klíčová slova: minipig; Huntington´s disease Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Evaluation of efficacy and bio-distribution of AAV5-miHTT in HD minipig brain

Healthy minipigs (n=29) were pre-screened for serum AAV5 neutralizing antibodies (NABs) in serum by uniQure. Conclusions: Intrastriatal/intrathalamic bilateral application of ...

Bohuslavová, Božena; Juhás, Štefan; Juhásová, Jana; Ellederová, Zdeňka; Motlík, Jan
Ústav živočišné fyziologie a genetiky, 2016

Phenotypic Analyses of the HD transgenic Minipig Model
Motlík, Jan; Ellederová, Zdeňka
2016 - anglický The transgenic model of Huntington’s disease in minipig (TgHD) was created in 2009 and information coding the sequence of N-terminal part of human mutated huntingtin was transferred to subsequent generations from both female and male sides. In each litter, transgenic (TgHD) and wild-type (WT) piglets were born in approximately equal ratio. At present, the Laboratory of Cell Regeneration and Plasticity keeps sets of animals in F2 and F3 generations with identical genetic background and bred in identical conditions of feeding and housing. The present research project was focused on a complex of non-invasive and invasive approaches to WT and TgHD minipigs to achieve the entire phenotypic analysis of HD progression in this large animal model. Klíčová slova: minipig Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Phenotypic Analyses of the HD transgenic Minipig Model

The transgenic model of Huntington’s disease in minipig (TgHD) was created in 2009 and information coding the sequence of N-terminal part of human mutated huntingtin was transferred to subsequent ...

Motlík, Jan; Ellederová, Zdeňka
Ústav živočišné fyziologie a genetiky, 2016

Mendel Forum 2014
Matalová, Eva; Matalová, A.
2014 - český Klíčová slova: Mendel Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Mendel Forum 2014

Matalová, Eva; Matalová, A.
Ústav živočišné fyziologie a genetiky, 2014

Metodika vypracování akutního a transgenního modelu Huntingtonovy choroby u miniaturních prasat a jeho aplikace pro testování nových léčebných postupů a léčiv v oblasti neurodegenerativních chorob
Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Vodička, Petr; Baxa, Monika
2014 - český Cílem metodiky je vypracování biomedicínského modelu Huntingtonovy choroby u miniaturních prasat a jeho využití v preklinické praxi pro testování nových léčebných postupů jak farmakologických, tak pomocí nových molekulárně biologických metod. The aim of this methodology is to develop a biomedical model of Huntington's disease in miniature pigs and its use in practice for preclinical testing of new treatments both pharmacological and using new molecular biological methods. Klíčová slova: Huntington´s disease Plné texty jsou dostupné na jednotlivých ústavech Akademie věd ČR. Metodika vypracování akutního a transgenního modelu Huntingtonovy choroby u miniaturních prasat a jeho aplikace pro testování nových léčebných postupů a léčiv v oblasti neurodegenerativních chorob

Cílem metodiky je vypracování biomedicínského modelu Huntingtonovy choroby u miniaturních prasat a jeho využití v preklinické praxi pro testování nových léčebných postupů jak farmakologických, tak ...

Motlík, Jan; Juhás, Štefan; Juhásová, Jana; Vodička, Petr; Baxa, Monika
Ústav živočišné fyziologie a genetiky, 2014