National Repository of Grey Literature 42 records found  1 - 10nextend  jump to record: Search took 0.01 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...
Manipulating the mammalian oocyte and embryo - Biological and epigenetic aspects
Fulková, Helena ; Hozák, Pavel (advisor) ; Hampl, Aleš (referee) ; Motlík, Jan (referee)
CONCLUSIONS . By antibodies against ďfferent covalent histone modifications and 5-methylcytosine, we have partialty characterised the epigenetic changes taking place during the oocyte mauration and in early mammalian embryogenesis in the mouse and pig, respectively. o We have also characterised thc epigenetic repogramming activities of cytoplasts derived from oocytes at different stages of maturation after somatic cell nuclear transfer. . We have evaluated the epigenetic effec$ of selected procedures that are currently used for embryo production. . Finally, we have developed a new cryopreservation scheme for oocyte nuclear material storage. orrr research is engaged in the development ofnew bíotechniques as well as elucidating and characterising the epigenetic pÍocesses that take place during normal and abnormal embryogenesis. Abnormal embryonic development is for example often observed in somatic cell nuclear transfer embryos. These techniques can also be potentially used not only in human medicine but also for valuable livestock and endangered species preservation Oy e.g. interspecies nuclear transfer). Especially in human meďcine, attention to the ethical issues associated with these techniques must be paid. It is also clear tbat many biological problems still do exist and these should not be...
Protein synthesis and protein degradation in mammalian oocyte development
Šušor, Andrej ; Motlík, Jan (advisor) ; Pěknicová, Jana (referee) ; Petr, Jaroslav (referee)
Concr,usroNs We anďysed eucaryoticinitiation t,anslation factorsthat are responsiblefor protein qmthesisin mammalianoocýes. As well we examinedthe affinity.of this factorsto.'mCap, Sepharoseduring in útro conďtion...Inour'laboratorywas optimisedthe protocol for generation of poreine parttrenotesthat serve us as a model for anďysis of. cellular processos in .rygotes with biochemical approaches.. : , , - Antibod}r micÍoanay analysis was used to investigate the: regulation of signalling pathways primarily during meiotic maturationof pig oocytesand subsequentlyin comparisonto other species(bovine,frog andseastar). on the base of proteomeanďysis of maturationof oocýes was chosenUCH-LI molebuleandis studiedin detail in mammalian oocyte. Abnost thorougily was analysed function of UCH-LI in porcine and bovine oocyte using specific inhibitors and overexpression. The mechanism that is involved UCH-LI in antipolyspermydefencein mammalian oocyte was unveiled in our laboratory.
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.
Double strand DNA breaks response in Huntington´s disease transgenic minipigs
Vaškovičová, Michaela ; Šmatlíková, Petra ; Herbert, A. ; Motlík, Jan ; Šolc, Petr
Huntington’s disease (HD) is progressive neurodegenerative disorder caused by presence of CAG expansion in the huntingtin gene, which gives rise to mutated form of huntingtin protein (mHtt). There is a strong evidence that DNA damage response is compromised by presence of mHtt in cells and increase of double strand DNA breaks (DSBs) is an early event in HD pathology. It was shown, that level of γH2AX is significantly higher in R6/2 mice compared to wild-type animals. Moreover, level of γH2AX is higher also in striatal neurons and fibroblasts of human HD patients. Furthermore, protein p53, key player in DNA damage response, is hyperactivated in cells expressing mHtt and inhibition of p53 or ATM ameliorates phenotypes of HD animal models. However, exact mechanism of mHtt action is not clear and therefore further investigation of mHtt effects on DSBs response is very important for the understanding of HD pathology.
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).

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