1. A Longitudinal Motor Characterisation of the HdhQ111 Mouse Model of Huntington’s Disease
- Author
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Stephen B. Dunnett, Emma Yhnell, and Simon Philip Brooks
- Subjects
0301 basic medicine ,Oncology ,Research Report ,Male ,medicine.medical_specialty ,Pathology ,Genotype ,mouse model ,Mice, Transgenic ,Nerve Tissue Proteins ,Disease ,Motor Activity ,Rotarod performance test ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,0302 clinical medicine ,Huntington's disease ,Internal medicine ,medicine ,Animals ,Humans ,Longitudinal Studies ,Muscle Strength ,Postural Balance ,Gait Disorders, Neurologic ,Balance (ability) ,Analysis of Variance ,Huntingtin Protein ,Body Weight ,Wild type ,Nuclear Proteins ,medicine.disease ,motor characterisation and longitudinal ,Transplantation ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Huntington Disease ,Gait analysis ,Rotarod Performance Test ,Mutation ,Sensation Disorders ,RC0321 ,Neurology (clinical) ,Analysis of variance ,Psychology ,030217 neurology & neurosurgery ,Huntington’s disease - Abstract
Background: Huntington’s disease (HD) is a rare, incurable neurodegenerative disorder caused by a CAG trinucleotide expansion with the first exon of the huntingtin gene. Numerous knock-in mouse models are currently available for modelling HD. However, before their use in scientific research, these models must be characterised to determine their face and predictive validity as models of the disease and their reliability in recapitulating HD symptoms.\ud Objective: Manifest HD is currently diagnosed upon the onset of motor symptoms, thus we sought to longitudinally characterise the progression and severity of motor signs in the HdhQ111 knock-in mouse model of HD, in heterozygous mice.\ud Methods: An extensive battery of motor tests including: rotarod, inverted lid test, balance beam, spontaneous locomotor activity and gait analysis were applied longitudinally to a cohort of HdhQ111 heterozygous mice in order to progressively assess motor function.\ud Results: A progressive failure to gain body weight was demonstrated from 11 months of age and motor problems in all measures of balance beam performance were shown in HdhQ111 heterozygous animals in comparison to wild type control animals from 9 months of age. A decreased latency to fall from the rotarod was demonstrated in HdhQ111 heterozygous animals in comparison to wild type animals, although this was not progressive with time. No genotype specific differences were demonstrated in any of the other motor tests included in the test battery.\ud Conclusions: The HdhQ111 heterozygous mouse demonstrates a subtle and progressive motor phenotype that begins at 9 months of age. This mouse model represents an early disease stage and would be ideal for testing therapeutic strategies that require elongated lead-in times, such as viral gene therapies or striatal transplantation.
- Published
- 2016