title: Novel ethological endophenotypes in a transgenic mouse model of Huntington's disease.
abstract: Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with a characteristic triad of cognitive, affective and motor symptoms. Transgenic HD mice show excellent construct and face validity for many of these symptoms, however the decline in some facets of every day activity in humans is difficult to model. One approach is the assessment of species-relevant behaviors. Here we described three ethologically appropriate tests in the mouse-olfactory sensitivity, nest-building and sexually-motivated vocalizations. In R6/1 HD mice, olfactory and nest-building tests were sensitive to early dysfunctions induced by the HD mutation. Male vocalization testing revealed a late-stage sexual disinterest in R6/1 HD mice compared to WT littermates. We show that essential, species-relevant functions are disrupted by the HD mutation. The development of integrative behavioral assays which more closely model 'activities of daily living' (ADL) will facilitate the testing of novel therapeutic interventions in animal models as well as their clinical translation.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Melbourne, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Melbourne, Australia. Electronic address: christina.mo@unimelb.edu.au.
authors.forename: Christina
authors.initials: C
authors.lastname: Mo
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Melbourne, Australia. Electronic address: tibo.renoir@gmail.com.
authors.forename: Thibault
authors.initials: T
authors.lastname: Renoir
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Kenneth Myer Building, University of Melbourne, Parkville, Melbourne, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Melbourne, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D058068:Endophenotypes; D004971:Estrus / Q000502:physiology; D005010:Ethology / Q000379:methods; D005260:Female; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009425:Nesting Behavior / Q000502:physiology; D055696:Olfactory Perception / Q000235:genetics / Q000502:physiology; D014556:Urine / Q000502:physiology; D014828:Vocalization, Animal
chemical_list: C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins
keywords: Ethological; Huntington's disease; Nest-building; Olfactory; Sexual; Vocalization