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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 - English
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.
Keywords:
minipigs; Huntington´s disease
Available at various institutes of the ASCR
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 ...
Evaluation of strategies for humanization of the entire porcine HTT locus
Vochozková, Petra; Klymiuk, N.; Wolf, E.; Ellederová, Zdeňka; Motlík, Jan
2017 - English
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).
Keywords:
minipig model; HTT locus
Available at various institutes of the ASCR
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 ...
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 - English
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.
Keywords:
mutant huntingtin
Available at various institutes of the ASCR
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 ...
Body fluid exosomes as potential carriers of Huntington’s disease biomarkers
Kupcová Skalníková, Helena; Červenka, Jakub; Bohuslavová, Božena; Turnovcová, Karolína; Vodička, Petr
2017 - English
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.
Keywords:
Huntington´s disease
Available at various institutes of the ASCR
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 ...
The effect of WNT5A and WNT7A on cartilage formation and anterior-posterior patterning of the limb
Killinger, Michael; Buchtová, Marcela
2017 - English
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.
Keywords:
limb
Available at various institutes of the ASCR
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 ...
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 - English
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.
Keywords:
rat; mouse
Available at various institutes of the ASCR
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 ...
E-INFRASTRUCTURES FOR RESEARCH AND INNOVATION: LINKING INFORMATION SYSTEMS TO IMPROVE SCIENTIFIC KNOWLEDGE PRODUCTION
Ráb, Petr
2012 - English
The workshop gives an overview about CRIS in the Czech Republic and Slovakia. It consists of a number of short presentations that mention important aspects and current question about CRIS in the two neighbouring countries. Research evaluation is among the important topics as well.
Keywords:
CRIS
Available at various institutes of the ASCR
E-INFRASTRUCTURES FOR RESEARCH AND INNOVATION: LINKING INFORMATION SYSTEMS TO IMPROVE SCIENTIFIC KNOWLEDGE PRODUCTION
The workshop gives an overview about CRIS in the Czech Republic and Slovakia. It consists of a number of short presentations that mention important aspects and current question about CRIS in the two ...
Effect of Palmitoylchitosan on Cholesterol Homeostatis in Rats
Marounek, Milan; Volek, Z.; Skřivanová, E.; Tůma, J.; Synytsya, A.
2010 - English
The association between plasma cholesterol and coronary hearth disease is well established; thus the possibility of plasma cholesterol reduction by interfering with the absorption of sterols in the intestine has been studied.
Keywords:
palmitoylchitosan; choelsterol; rat
Available at various institutes of the ASCR
Effect of Palmitoylchitosan on Cholesterol Homeostatis in Rats
The association between plasma cholesterol and coronary hearth disease is well established; thus the possibility of plasma cholesterol reduction by interfering with the absorption of sterols in the ...
Amphibians recorded in the Bamenda Highlands, Cameroon
Gvoždík, Václav
2010 - English
An endemics species of Amphibians were recorded in the Bamenda Highlands, Cameroon.
Keywords:
Amphibians; Cameroon
Available at various institutes of the ASCR
Amphibians recorded in the Bamenda Highlands, Cameroon
An endemics species of Amphibians were recorded in the Bamenda Highlands, Cameroon.
Proteomics of CDK inhibition in cancer cells
Kovářová, Hana; Skalníková, Helena; Halada, Petr; Strnad, M.; Hajdúch, M.
2007 - English
In order to improve our understanding of the biochemical basis of the anti-cancer activity of olomoucine-derived synthetic cyclin-dependent kinase inhibitors (CDKIs) and to search for novel proteins associated with these biological effects we applied complex proteomic approaches. To analyse cellular responses to the CDKI we used two cancer models: the CEM T-lymphoblastic leukemia cell line representing hematological malignancy, and the A549 lung adenocarcinoma cell line as a solid tumor model. Cancer cells of these lines were cultured in both the presence and absence (controls) of the CDKI, bohemine (BOH). Cellular proteins of both of these lines were then extracted and fractionated using conventional two-dimensional gel electrophoresis (2-DE), and for the CEM T-lymphoblastic leukemia cell line we also used a 2-D liquid phase fractionation system ProteomeLab PF 2D ( Beckman Coulter). Computer-assisted data analysis of the resulting 2-D protein expression maps was applied to determine the similarity/dissimilarity of the maps and to select characteristic protein spots or bands based on the quantitative differences between BOH-treated and control cells. Many of these differentially expressed proteins were identified by mass spectrometry, since they represent candidate biomarkers of cancer cell responses to CDK inhibition and cellular pathways that are relevant to the anti-cancer activity of the CDKIs. Subsequently, we focused directly on these proteins in confirmatory studies using various techniques (including quantitative immunoblotting, immunocytochemistry and functional activity analyses) to demonstrate the validity of the proteomic results and extend our knowledge of the CDKI effects. Využíváme komplexního proteomického přístupu pro studium biochemického principu protinádorového účinku syntetických inhibitorů cyklin dependentních kináz (CDKI) a pro hledání nových proteinů asociovaných s těmito biologickými účinky. Nádorové buňky dvou buněčných linií reprezentujících hematologickou malignitu a solidní tumor kultivujeme v přítomnosti nebo absenci CDKI Boheminu. Celulární proteiny těchto linií extrahujeme a frakcionujeme pomocí klasické dvourozměrné gelové chromatografie a take pomocí dvourozměrné kapalinové chromatografie (systém PF2D) Získané proteinové mapy počítačově vyhodnocujeme a diferenční proteiny identifikujeme hmotnostní spektrometrií. Tyto proteiny jsou kandidátními biomarkery protinádorové odpovědi na inhibici cyklin dependentních kináz.
Keywords:
cyclin-dependent kinase inhibitors; cancer; proteomics
Available at various institutes of the ASCR
Proteomics of CDK inhibition in cancer cells
In order to improve our understanding of the biochemical basis of the anti-cancer activity of olomoucine-derived synthetic cyclin-dependent kinase inhibitors (CDKIs) and to search for novel proteins ...
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