title: Behavioral phenotyping of minipigs transgenic for the Huntington gene.
abstract: 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 behavioral phenotype of a transgenic (tg) HD minipig model.
  
  
  
  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 color discrimination test, (5) a startbox back and forth test and (6) a dominance test. Performance of all tests and definition of measures obtained is presented.
  
  
  
  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.
  
  
  
  So far there are no established or validated assessments to test minipigs in the domains described.
  
  
  
  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 behavioral features of tg and wt minipigs.
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany; Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Bischofsholer Damm 15 30173, Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schramke
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Schuldenzucker
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany.
authors.forename: Robin
authors.initials: R
authors.lastname: Schubert
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany; Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, v.v.i., AS CR, Libechov, Czech Republic.
authors.forename: Frauke
authors.initials: F
authors.lastname: Frank
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Wirsig
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Ott
authors.affiliation: Laboratory of Cell Regeneration and Plasticity, Institute of Animal Physiology and Genetics, v.v.i., AS CR, Libechov, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Motlik
authors.affiliation: Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Bischofsholer Damm 15 30173, Hannover, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fels
authors.affiliation: Institute for Animal Hygiene, Animal Welfare and Farm Animal Behaviour, University of Veterinary Medicine Hannover, Bischofsholer Damm 15 30173, Hannover, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Kemper
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Hölzner
authors.affiliation: George-Huntington-Institute, Technology Park Muenster, Johann-Krane Weg 27 48149, Muenster, Germany; Department of Radiology, Universitaetsklinikum Muenster, Albert-Schweitzer Campus 1 48149, Muenster, Germany; Dept of Neurology Muenster, Germany; Department of Neurodegenerative Diseases and Hertie-Institute for Clinical Brain Research, University of Tuebingen, Hoppe-Seyler Str. 3 72076 Tuebingen, Germany. Electronic address: ralf.reilmann@ghi-muenster.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Reilmann
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D055253:Color Vision / Q000502:physiology; D004192:Discrimination, Psychological / Q000502:physiology; D004195:Disease Models, Animal; D004867:Equipment Design; D005240:Feasibility Studies; D005260:Female; D005684:Gait / Q000502:physiology; D006801:Humans; D000071058:Huntingtin Protein / Q000235:genetics* / Q000378:metabolism; D006816:Huntington Disease / Q000235:genetics; D007858:Learning / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009483:Neuropsychological Tests; D010641:Phenotype; D013552:Swine; D013556:Swine, Miniature / Q000235:genetics / Q000502:physiology / Q000523:psychology*; D014059:Tongue / Q000503:physiopathology
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein
keywords: Animal models; Behavioral; Cognitive; Minipig; Motor; Phenotyping; Preclinical research