Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation

Carter, R. J., Lione, L. A., Humby, Trevor ORCID: https://orcid.org/0000-0002-1840-1799, Mangiarini, L., Mahal, A., Bates, G. P., Dunnett, Stephen Bruce ORCID: https://orcid.org/0000-0003-1826-1578 and Morton, A. J. 1999. Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. The Journal of Neuroscience 19 (8) , pp. 3248-3257.

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Abstract

Transgenic mice expressing exon 1 of the human Huntington’s disease (HD) gene carrying a 141–157 CAG repeat (line R6/2) develop a progressive neurological phenotype with motor symptoms resembling those seen in HD. We have characterized the motor deficits in R6/2 mice using a battery of behavioral tests selected to measure motor aspects of swimming, fore- and hindlimb coordination, balance, and sensorimotor gating [swimming tank, rotarod, raised beam, fore- and hindpaw footprinting, and acoustic startle/prepulse inhibition (PPI)]. Behavioral testing was performed on female hemizygotic R6/2 transgenic mice (n = 9) and female wild-type littermates (n = 22) between 5 and 14 weeks of age. Transgenic mice did not show an overt behavioral phenotype until around 8 weeks of age. However, as early as 5–6 weeks of age they had significant difficulty swimming, traversing the narrowest square (5 mm) raised beam, and maintaining balance on the rotarod at rotation speeds of 33–44 rpm. Furthermore, they showed significant impairment in prepulse inhibition (an impairment also seen in patients with HD). Between 8 and 15 weeks, R6/2 transgenic mice showed a progressive deterioration in performance on all of the motor tests. Thus R6/2 mice show measurable deficits in motor behavior that begin subtly and increase progressively until death. Our data support the use of R6/2 mice as a model of HD and indicate that they may be useful for evaluating therapeutic strategies for HD, particularly those aimed at reducing the severity of motor symptoms or slowing the course of the disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Psychology
Subjects:	B Philosophy. Psychology. Religion > BF Psychology R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	transgenic mice; Huntington’s disease; CAG repeat; motor behavior; prepulse inhibition; sensorimotor gating; polyglutamine repeat diseases
Additional Information:	Pdf uploaded in accordance with publisher's policy at http://www.jneurosci.org/site/misc/ifa_policies.xhtml#copyright (accessed 27/02/2014).
Publisher:	Society for Neuroscience
ISSN:	0270-6474
Date of First Compliant Deposit:	30 March 2016
Last Modified:	03 May 2023 14:59
URI:	https://orca.cardiff.ac.uk/id/eprint/35355

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