Effects of Pin1 Loss in Hdh(Q111) Knock-in Mice.

ABSTRACT: Huntington's disease (HD) is a fatal, dominantly inherited, neurodegenerative disorder due to a pathological expansion of the CAG repeat in the coding region of the HTT gene. In the quest for understanding the molecular basis of neurodegeneration, we have previously demonstrated that the prolyl isomerase Pin1 plays a crucial role in mediating p53-dependent apoptosis triggered by mutant huntingtin (mHtt) in vitro. To assess the effects of the lack of Pin1 in vivo, we have bred Pin1 knock-out mice with Hdh(Q111) knock-in mice, a genetically precise model of HD. We show that Pin1 genetic ablation modifies a portion of Hdh(Q111) phenotypes in a time-dependent fashion. As an early event, Pin1 activity reduces the DNA damage response (DDR). In midlife mice, by taking advantage of next-generation

SUBMITTER: Agostoni E 

PROVIDER: S-EPMC4852193 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature