Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study

PLoS One. 2017 Oct 9;12(10):e0185970. doi: 10.1371/journal.pone.0185970. eCollection 2017.


Background: Large animal models of Huntington's disease (HD) may increase the reliability of translating preclinical findings to humans. Long live expectancy offers opportunities particularly for disease modifying approaches, but also challenges. The transgenic (tg) HD minipig model assessed in this study exhibits a high genetic homology with humans, similar body weight, and comparable brain structures. To test long-term safety, tolerability, and efficacy of novel therapeutic approaches in this model reliable assessments applicable longitudinally for several years are warranted for all phenotypical domains relevant in HD.

Objective: To investigate whether the tests proposed assessing motor, cognitive and behavioral domains can be applied repetitively over a 3-year period in minipigs with acceptable variability or learning effects and whether tgHD minipigs reveal changes in these domains compared to wildtype (wt) minipigs suggesting the development of an HD phenotype.

Methods: A cohort of 14 tgHD and 18 wt minipigs was followed for three years. Tests applied every six months included a tongue coordination and hurdle test for the motor domain, a color discrimination test for cognition, and a dominance test for assessing behavior. Statistical analyses were performed using repeated ANOVA for longitudinal group comparisons and Wilcoxon-tests for intra-visit differences between tgHD and wt minipigs.

Results: All tests applied demonstrated feasibility, acceptable variance and good consistency during the three-year period. No significant differences between tgHD and wt minipigs were detected suggesting lack of a phenotype before the age of four years.

Conclusions: The assessment battery presented offers measures in all domains relevant for HD and can be applied in long-term phenotyping studies with tgHD minipigs. The observation of this cohort should be continued to explore the timeline of phenotype development and provide information for future interventional studies.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal / physiology*
  • Female
  • Humans
  • Huntingtin Protein / genetics
  • Huntingtin Protein / physiology
  • Huntington Disease / physiopathology*
  • Learning / physiology
  • Swine / physiology*
  • Swine, Miniature / physiology*
  • Tongue / physiology


  • Huntingtin Protein

Grants and funding

The George-Huntington-Institute has received grant support from the CHDI Foundation ( to conduct the work reported in this study to RR. We are grateful for additional relevant support provided by private donations of families affected by HD that would like to remain anonymous. The authors are not aware of any competing interests of these donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors declare no other financial interests related to this manuscript.