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Interplay between mutated huntingtin and precancerogenous status in mammalian cells.
Butalová, Nikola
;
Baxa, Monika
(advisor) ;
Koudelková, Lenka
(referee)
Huntington's disease is a serious hereditary disorder that causes mortification of neurons. The disease affects individuals around the age of 40. Its characteristics are involuntary movement of the limbs and a progressive dementia. This disorder is currently without any treatment and always ends with patient dying within a period of 15 years after the first symptoms are discovered. Special relation between Huntington's disease and malign neoplasia was observed at the end of the 20th century. This relation shows lower degree of cancer among the patients with this neurodegenerative disorder compared to the general population. An expanded sequence of a CAG section probably protects these persons against advancement of cancer. Creation of an applicable experimental model with characteristic highly resembling human body was necessary for superior research of this disease. This model can be represented by a transgene mini pig carrying a mutated protein huntingtin - tgHD pig. Another model of a mini-pig showing hereditary occurrence of malign lesions - MeLiM pig was created to research cancer. These two specific lines of mini-pigs were crossbred resulting in not only piglets with melanoma and transgene piglets with mtHTT but also transgene piglets having melanoma at the same time. Furthermore the same...
Detailed record
Characterization of immune cells and monitoring changes of inflammatory proteins in minipig model of Huntington's disease
Butalová, Nikola
;
Motlík, Jan
(advisor) ;
Janda, Jozef
(referee)
The Huntington disease (HD) is a hereditary neuro-degenerative disorder caused by a mutation of the huntigtin gene that codes a protein of the same name. The mutated form of the huntigtin gene plays its part in many pathological interactions and influences a number of cellular mechanisms, including the immune system that could serve as a modifier of the neuropathology of the disease. The cells of the monocyte-macrophage system express cytokines whose production changes in relation to the activation of the cell. The presence of the mutated huntingtin protein in these cells renders them hyper-responsive to immunity incentives leading to changes in the production of cytokines. These differences are discernible a few years prior to the appearance of the symptoms. Therefore, the changes in the levels of certain cytokines could serve as appropriate biomarkers for monitoring of the onset of the disease and its progression. The HD pathogenesis includes an inflammation of the central neutral system. Inflammatory changes in peripheral tissues could reflect inflammatory processes in the central neural system. A miniature TgHD pig could represent an appropriate model organism for studying of the impact of the mHtt on the immune system. This model enables to observe a slow progression of the disease. Changes in...
Detailed record
Interplay between mutated huntingtin and precancerogenous status in mammalian cells.
Butalová, Nikola
;
Baxa, Monika
(advisor) ;
Koudelková, Lenka
(referee)
Huntington's disease is a serious hereditary disorder that causes mortification of neurons. The disease affects individuals around the age of 40. Its characteristics are involuntary movement of the limbs and a progressive dementia. This disorder is currently without any treatment and always ends with patient dying within a period of 15 years after the first symptoms are discovered. Special relation between Huntington's disease and malign neoplasia was observed at the end of the 20th century. This relation shows lower degree of cancer among the patients with this neurodegenerative disorder compared to the general population. An expanded sequence of a CAG section probably protects these persons against advancement of cancer. Creation of an applicable experimental model with characteristic highly resembling human body was necessary for superior research of this disease. This model can be represented by a transgene mini pig carrying a mutated protein huntingtin - tgHD pig. Another model of a mini-pig showing hereditary occurrence of malign lesions - MeLiM pig was created to research cancer. These two specific lines of mini-pigs were crossbred resulting in not only piglets with melanoma and transgene piglets with mtHTT but also transgene piglets having melanoma at the same time. Furthermore the same...
Detailed record
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