Behavioral phenotyping of minipigs transgenic for the Huntington gene
Language English Country Netherlands Media print-electronic
Document type Journal Article
PubMed
26688470
DOI
10.1016/j.jneumeth.2015.11.013
PII: S0165-0270(15)00415-X
Knihovny.cz E-resources
- Keywords
- Animal models, Behavioral, Cognitive, Minipig, Motor, Phenotyping, Preclinical research,
- MeSH
- Behavior, Animal * MeSH
- Gait physiology MeSH
- Equipment Design MeSH
- Discrimination, Psychological physiology MeSH
- Phenotype MeSH
- Animals, Genetically Modified * MeSH
- Huntington Disease genetics MeSH
- Tongue physiopathology MeSH
- Humans MeSH
- Swine, Miniature genetics physiology psychology MeSH
- Disease Models, Animal * MeSH
- Neuropsychological Tests MeSH
- Motor Activity physiology MeSH
- Swine MeSH
- Huntingtin Protein genetics metabolism MeSH
- Feasibility Studies MeSH
- Learning physiology MeSH
- Color Vision physiology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- HTT protein, human MeSH Browser
- Huntingtin Protein MeSH
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 behavioral phenotype of a transgenic (tg) HD minipig model. NEW 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 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. 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. COMPARISON WITH EXISTING METHOD(S): So far there are no established or validated assessments to test minipigs in the domains described. 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 behavioral features of tg and wt minipigs.
References provided by Crossref.org
Large Animal Models of Huntington's Disease: What We Have Learned and Where We Need to Go Next
Behavioral testing of minipigs transgenic for the Huntington gene-A three-year observational study
