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C11 Behavioural studies in Libechov minipigs with huntington’s disease; changes in behaviour, motor skills and learning
  1. Bozena Bohuslavova1,2,
  2. Sarka Kucerova1,2,
  3. Monika Macakova1,2,
  4. Jiri Klempir3,
  5. Romana Lavickova3,
  6. Radim Krupicka4,
  7. Jan Kauler4,
  8. Monika Baxa1,2,
  9. Zdenka Ellederova1,
  10. Jan Motlik1
  1. 1Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Czech Academy of Science, Libechov, Czech Republic
  2. 2Department of Cell Biology, Faculty of Science, Charles University in Prague, Czech Republic
  3. 3Department of Neurology and Centre of Clinical Neuroscience, 1st Faculty of Medicine, Charles University and General University Hospital in Prague, Czech Republic
  4. 4Department of Biomedical Informatics, Faculty of Biomedical Engineering, Czech Technical University in Prague, Czech Republic

Abstract

Background Huntington’s disease (HD) is characterised by involuntary chorea like movements, poor balance, slurred speech, difficulty swallowing, personality change and difficulty thinking manifesting in the middle age of the patients. Changes in behaviour, motor skills and learning correlate with progression of the disease. Thus it is necessary to monitor these changes in new animal models. In 2009, we have generated transgenic minipigs (TgHD) expressing N-terminal (548 aa) part of human huntingtin (Htt) containing 126 CAG/CAA repeats.

Aims To follow disease development in TgHD minipigs of F0, F1 and F3 generation using motoric and behavioural tests.

Methods In order to follow behavioural and motoric changes we introduced stability pull back test, balance bean, seesaw test, up and down step test, and tunnel test. We also initiated to use accelerometers to monitor walking differences.

Results We observed higher fear or inability to perform certain tests, delayed learning period mainly in situations inducing stress in our oldest TgHD animals (F0, F1 generations). The significant difference between WT and TgHD minipigs was noticed in the ability to step on and to cross the elevated balance beam. Pull back stability test showed a significant difference in TgHD animals. Wobbly movements of back legs were observed in the five years old animals. The weight of all the oldest animals dropped in 10% in the last year.

Conclusions The minipig model starts to show a motoric impairment phenotype, and thus to be a promising model for preclinical testing of new therapeutic approaches of HD.

Acknowledgement “The research leading to these results has received funding from the Norwegian Financial Mechanism 2009–2014 and the Ministry of Education, Youth and Sports Project under Contract no. MSMT-28477/2014” (7F14308/2014), and National Sustainability Programme, project number LO1609 (Czech Ministry of Education, Youth and Sports) and RVO: 67985904

  • behaviour
  • minipig model
  • phenotype

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