Behavioral phenotyping of minipigs transgenic for the Huntington gene

• Published in: Journal of neuroscience methods 2016-05, Vol.265, p.34-45
• Main Authors: Schramke, Sarah, Schuldenzucker, Verena, Schubert, Robin, Frank, Frauke, Wirsig, Maike, Ott, Stefanie, Motlik, Jan, Fels, Michaela, Kemper, Nicole, Hölzner, Eva, Reilmann, Ralf
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Animals, Genetically Modified; Behavior, Animal; Behavioral; Cognitive; Color Vision - physiology; Discrimination (Psychology) - physiology; Disease Models, Animal; Equipment Design; Feasibility Studies; Female; Gait - physiology; Humans; Huntingtin Protein - genetics; Huntingtin Protein - metabolism; Huntington Disease - genetics; Learning - physiology; Minipig; Motor; Motor Activity - physiology; Neuropsychological Tests; Phenotype; Phenotyping; Preclinical research; Swine; Swine, Miniature - genetics; Swine, Miniature - physiology; Swine, Miniature - psychology; Tongue - physiopathology
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2015.11.013

•Large animal models such as minipigs provide new options for research in HD.•Their long lifespan resembles human HD calling for sensitive phenotype assessments.•Motor, cognitive and behavioral tests to assess the phenotype of minipigs are proposed.•We demonstrate feasibility to perform these assessments in tgHD minipigs.•The tests proposed facilitate observational and interventional trials in tgHD minipigs. 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.