Double strand DNA breaks response in Huntington´s disease transgenic minipigs

0485176 - ÚŽFG 2018 CZ eng K - Konferenční příspěvek (tuzemská konf.)
Vaškovičová, Michaela - Šmatlíková, Petra - Herbert, A. - Motlík, Jan - Šolc, Petr
Double strand DNA breaks response in Huntington´s disease transgenic minipigs.
The 4th Animal Models of Neurodegenerative Diseases. Liběchov: ÚŽFG AV ČR, v. v. i., 2017, s. 30-31.
[Animal Models of Neurodegenerative Diseases /4./. Liblice (CZ), 22.10.2017-24.10.2017]
Grant CEP: GA MŠMT(CZ) LO1609; GA MŠMT 7F14308
Institucionální podpora: RVO:67985904
Klíčová slova: transgenic minipigs
Obor OECD: Technologies involving identifying the functioning of DNA, proteins and enzymes and how they influence the onset of disease and maintenance of well-being (gene-based diagnostics and therapeutic interventions (pharmacogenomics, gene-based therapeutics)

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.
Trvalý link: http://hdl.handle.net/11104/0280251