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C10 Behavioural phenotyping of minipigs transgenic for the huntington gene
  1. Verena Schuldenzucker1,2,
  2. Robin Schubert1,
  3. Frauke Freisfeld1,3,
  4. Lorena Rieke1,
  5. Tamara Matheis1,
  6. Jan Motlik4,
  7. Sarah Schramke1,
  8. Ralf Reilmann1,3,5
  1. 1George-Huntington-Institute, Technology-Park, Muenster, Germany
  2. 2Institute of Zoology, University of Veterinary Medicine Hannover, Hannover, Germany
  3. 3Department of Clinical Radiology, University of Muenster, Muenster, Germany
  4. 4Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, Libechov, Czech Republic
  5. 5Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany

Abstract

Background While several novel therapeutic approaches for HD are in development, resources to conduct clinical trials are limited. Large animal models have been proposed to improve assessment of safety, tolerability and especially to increase translational reliability of efficacy signals obtained in preclinical studies. They may thus help to select candidates for translation to human studies. We here introduce a battery of novel tests designed to assess the motor, cognitive and behavioural phenotype of a transgenic (tg) HD minipig model.

Methods A group of tgHD and wildtype (wt) Libechov minipigs (n = 36) was available for assessment with (1) a gait test using the GAITRite® automated acquisition system, (2) a hurdle-test, (3) a tongue coordination test, (4) a startbox back and forth test and (5) a dominance test. Performance of all tests and definition of measures obtained is presented.

Results Minipigs were able to learn performance of all tests. All tests were safe, well tolerated and feasible. Exploratory between group comparisons showed no differences between groups of tgHD and wt minipigs assessed, but low variability within and between groups.

Conclusions The data shows that the tests presented are safe, well tolerated and all measures defined can be assessed. Prospective longitudinal application of these tests is warranted to determine their test-retest reliability, sensitivity and validity in assessing motor, cognitive and behavioural features of tg and wt minipigs.

Acknowledgement Funded by the CHDI Foundation.

  • animal models
  • minipig
  • HD
  • phenotyping
  • behavioural
  • preclinical research

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