Ústav živočišné fyziologie a genetiky

Ústav živočišné fyziologie a genetiky Nalezeno 89 záznamů.  předchozí11 - 20dalšíkonec  přejít na záznam: Hledání trvalo 0.00 vteřin. 
Oxidative stress in primary porcine fibroblasts expressing mutated huntingtin
Šmatlíková, Petra ; Askeland, G. ; Vaškovičová, Michaela ; Klíma, Jiří ; Motlík, Jan ; Eide, L. ; Ellederová, Zdeňka
Molecular events, such as protein aggregation, mitochondrial dysfunction, and transcriptional dysregulation have been linked to Huntington’s disease (HD) pathogenesis. Oxidative stress has been considered as one of the key players in disease progression. Though, it is still not clear whether oxidative stress causes HD, or if it is a consequence of other primary events.
Mitochondrial phenotype in minipig model transgenic for N-terminal part of human mutated huntingtin
Hansíková, H. ; Rodinová, M. ; Křížová, J. ; Dosoudilová, Z. ; Štufková, H. ; Bohuslavová, Božena ; Klíma, Jiří ; Juhás, Štefan ; Ellederová, Zdeňka ; Motlík, Jan ; Zeman, J.
Huntington’s disease (HD) is neurodegenerative disorder caused by an abnormal expansion of CAG repeat encoding a polyglutamine tract of huntingtin (htt). It has been postulated that mitochondria dysfunction may play significant role in the pathophysiology of the HD. But it is still not known yet in detail how mitochondria are able to cover energy needs of the cells during the progression of the HD.
Evaluation of strategies for humanization of the entire porcine HTT locus
Vochozková, Petra ; Klymiuk, N. ; Wolf, E. ; Ellederová, Zdeňka ; Motlík, Jan
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).
Establishing preclinical proof-of-concept of gene therapy for Huntington disease
Miniariková, J. ; Juhás, Štefan ; Caron, N. ; Spronck, L. ; Vallés, A. ; De Haan, M. ; Blits, B. ; Ellederová, Zdeňka ; van Deventer, S. ; Petry, H. ; Southwell, A. ; Déglon, N. ; Motlík, Jan ; Konstantinová, P. ; Evers, M.
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HTT gene. The translated expanded polyglutamine repeat in the huntingtin protein is known to cause toxic gain-of-function, affecting numerous cellular processes. Our approach involves a new therapeutic modality by developing a single (one-time) treatment for HD based on a gene therapy lowering the expression of the toxic huntingtin using the RNA interference (RNAi) mechanism. Huntingtin lowering is achieved using gene transfer of a cassette encoding an engineered microRNA targeting human HTT, delivered via adeno-associated viral vector serotype 5 (AAV5-miHTT).
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.
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.
AAV-mediated delivery in large animals
Blits, B. ; De Haan, M. ; Evers, M. ; Spronck, E. A. ; Motlík, Jan ; Bohuslavová, Božena ; Ellederová, Zdeňka ; Lewis, O. T. ; Johnson, D. ; Woolley, M. ; Gill, S. ; van Deventer, S. ; Konstantinová, P. ; Petry, H.
Gene therapy is an attractive option for treatment of neurological diseases. Delivery of the therapeutic gene at the proper location is key for an effective treatment and remains challenging, especially in larger animals. For translation from smaller (rodents) to larger animals, dimensions are different, but also the immune system plays a more prominent role in larger animals. Direct intracranial parenchymal infusions usually result in local transduction of tissue, whereas intrathecal infusions result in a more widespread transduction in the brain. Depending on the indication, the desired expression pattern of the therapeutic gene is to be elucidated and is dictating the route of infusion.
Body fluid exosomes as potential carriers of Huntington’s disease biomarkers
Kupcová Skalníková, Helena ; Červenka, Jakub ; Bohuslavová, Božena ; Turnovcová, Karolína ; Vodička, Petr
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.
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.
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.
Role of planar cell polarity pathway in ameloblastoma with focus on frizzled 6
Putnová, Barbora ; Putnová, Iveta ; Hrubá, Eva ; Dosedělová, Hana ; Štembírek, Jan ; Daněk, Z. ; Buchtová, Marcela
Ameloblastoma is the most common epithelial odontogenic tumour in the oral cavity. Its progression is usually slow and the surface is covered by an oral mucosa with physiologic appearance. These tumours do not cause any pain to the patient and therefore it is difficult to diagnose them on time and the first signs are often missed by clinician leading to late diagnosis.
Mechanism of complex tooth shape development in reptiles
Landová, Marie ; Zahradníček, Oldřich ; Dosedělová, Hana ; Kavková, M. ; Zikmund, T. ; Buchtová, Marcela
Tooth shape formation in mammals is well known proces thanks to the broad studies on the mouse molars. The main role in regulation of this proces plays the enamel knot. Enamel knots are formed by cluster of cells, which serves as a source of numerous signalling molecules such as SHH or members of WNT, BMP and FGF families. Almost all our knowledge about teeth came from study on the mouse model. For better understanding of odontogenesis, it is however necessary to compare developmental processes to another species. One of the most heterogenic group of dentition type and shape are reptiles. How the shape of their teeth completed is still unknown. Aim of our study is therefore to uncover developmental processes involved in cusp formation in non-mammalian species with focus on reptiles. As model species for this study, we selected chameleons where multicuspis teeth develop in the caudal area of the jaw.

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