Longitudinal analysis of the behavioural phenotype in Hdh(CAG)150 Huntington's disease knock-in mice

Brooks, Simon Philip ORCID: https://orcid.org/0000-0001-9853-6177, Higgs, Gemma, Jones, Lesley ORCID: https://orcid.org/0000-0002-3007-4612 and Dunnett, Stephen Bruce ORCID: https://orcid.org/0000-0003-1826-1578 2012. Longitudinal analysis of the behavioural phenotype in Hdh(CAG)150 Huntington's disease knock-in mice. Brain Research Bulletin 88 (2-3) , pp. 182-188. 10.1016/j.brainresbull.2010.05.004

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Abstract

In people with Huntington's disease, an expanded CAG repeat sequence on the HTT gene confers a toxic gain function resulting in a progressive and fatal neurodegeneration. The Hdh(CAG)Q150 Huntington's disease mouse line is a knock-in model of the disease that carries approximately 150 CAG repeats on the normal mouse Htt locus. To determine that these mice are a useful model of the disease, they were assessed longitudinally for motor and cognitive deficits relevant to the human disease state. Each test was conducted bi-monthly across the lifespan of the animal. The results indicate that the Hdh(Q150/Q150) mice were impaired on each of the measures used, with deficits appearing on a 3-stage water maze test at 4 months of age and on prepulse inhibition at 6 months of age, both of which were prior to the manifestation of motor abnormalities. Grip strength, as measured by the inverted cage lid test, was reduced in the Hdh(Q150/Q150) mice from 10 months of age, when the male mice also exhibited weight loss relative to their wildtype littermates. On the accelerating rotarod, deficits in the carrier mice did not appear until they were 21 months old. Our results demonstrate that the Hdh(CAG)150 is a valid model of HD that displays early and progressive cognitive deficits that precede the onset of motor abnormalities.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Huntington's disease; Knock-in; HdhQ150; Behaviour; Phenotype; Cognitive; Motor
Publisher:	Elsevier
ISSN:	0361-9230
Related URLs:	http://www.ncbi.nlm.nih.gov/pubmed/20457...
Last Modified:	11 Mar 2023 02:33
URI:	https://orca.cardiff.ac.uk/id/eprint/19490

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