Background Huntington´s disease (HD) is devastating neurodegenerative disorder caused by the mutation in huntingtin gene. One of the largest contributors to HD pathology represents oxidative stress, though the exact mechanism of its cause remains unclear. Molecular characterization of a unique porcine model of HD could serve for better understanding of the disease pathogenesis as well as for better evaluation of the therapeutic efficiency of preclinical studies on this large animal model.

Aims In this study, we focused on the investigation of molecular and cellular features of fibroblasts isolated from transgenic minipigs expressing N-terminal part of human mutated huntingtin (TgHD) and the wild type (WT) siblings at different age, pre-symptomatic 24–36 months old and with starting behavioural symptoms at the age of 48 months.

Methods We investigated the levels of oxidative stress, the expression of oxidative stress related genes, proliferation capacity along with the expression of cyclin B1 and D1 proteins, cellular permeability, as well as nuclear and mitochondrial DNA damage in these cells.

Results TgHD fibroblasts isolated from 48 months old animals showed elevated levels of oxidative stress, overexpression of SOD2 gene, encoding a key mitochondria antioxidant, and NEIL3 gene, encoding DNA glycosylase involved in replication associated repair of DNA damaged by oxidative stress. These cells also displayed aberrant proliferation capacity and permeability. We further demonstrated preceded increased level of nuclear DNA damage in TgHD fibroblasts (isolated from 24–36 months old animals) indicating earlier aging of these cells.

Conclusions Our results suggest the age of 48 months of TgHD minipig model to be a breakpoint in developing molecular phenotype of HD along with changes in behaviour. Furthermore, this work proposes TgHD minipigs as a suitable large animal model for studying molecular mechanisms occurring gradually in HD pathophysiology with age.