National Repository of Grey Literature 6 records found  Search took 0.00 seconds. 
Phenotypic study Huntington's disease TgHD minipigs: Appearance and progress of reproductive and biochemical changes
Bohuslavová, Božena ; Motlík, Jan (advisor) ; Roth, Jan (referee) ; Petr, Jaroslav (referee) ; Krylov, Vladimír (referee)
Huntington's disease (HD) is one of the incurable and fatal diseases. HD belongs to the monogenic neurodegenerative diseases. According to the number of the CAG repetitions in the gene coding huntingtin, the onset of the disease is in childhood (5%), in the middle age, which is the most common (90%) and in the older age (5%). Beginning of the disease is manifested by changes in behavior; including problems with coordination and movement. Later, there is a psychological change. The disease leads to death. Until now, there is no effective curative treatment. In 2009, we created a model of the transgenic minipigs (TgHD) carrying the N - terminal part of the human mutant huntingtin (mtHtt) at our Institute in Liběchov. The number of offsprings and the resemblance in physiology and morphology between the pig (Sus scrofa) and humans (Homo sapiens) give us opportunities not only to study changes not only in central nerve organs, but also in peripheral tissues. The reproductive problems of TgHD boars were observed as the first phenotypic changes. Therefore, my work focuses at first on a study of the reproduction parameters of TgHD boars as well as ultrastructural, immunocytochemical and biochemical changes in testes and spermatozoa. In PhD thesis, I described in details the reproductive defects in TgHD...
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
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.
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.
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.
Evaluation of efficacy and bio-distribution of AAV5-miHTT in HD minipig brain
Bohuslavová, Božena ; Juhás, Štefan ; Juhásová, Jana ; Ellederová, Zdeňka ; Motlík, Jan
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.

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