24
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          jneurosci
          J. Neurosci
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          15 April 1999
          : 19
          : 8
          : 3248-3257
          Affiliations
          [ 1 ]Department of Pharmacology,
          [ 2 ]Centre for Brain Repair,
          [ 3 ]Parke-Davis Neuroscience Research, and
          [ 4 ]Department of Experimental Psychology, University of Cambridge, Cambridge, CB2 1QJ, United Kingdom, and
          [ 5 ]Division of Medical and Molecular Genetics, Guy’s Hospital, London SE1 9RT, United Kingdom
          Article
          PMC6782264 PMC6782264 6782264 2946
          10.1523/JNEUROSCI.19-08-03248.1999
          6782264
          10191337
          99da0489-d7f0-494c-ab22-75c2f7052c38
          Copyright © 1999 Society for Neuroscience
          History
          : 13 November 1998
          : 26 January 1999
          : 8 February 1999
          Categories
          Article
          Custom metadata
          5.00

          prepulse inhibition,polyglutamine repeat diseases,transgenic mice,sensorimotor gating,motor behavior,CAG repeat,Huntington’s disease

          Comments

          Comment on this article