RT Journal Article
SR Electronic
T1 Characterization of Progressive Motor Deficits in Mice Transgenic for the Human Huntington’s Disease Mutation
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3248
OP 3257
DO 10.1523/JNEUROSCI.19-08-03248.1999
VO 19
IS 8
A1 Rebecca J. Carter
A1 Lisa A. Lione
A1 Trevor Humby
A1 Laura Mangiarini
A1 Amarbirpal Mahal
A1 Gillian P. Bates
A1 Stephen B. Dunnett
A1 A. Jennifer Morton
YR 1999
UL http://www.jneurosci.org/content/19/8/3248.abstract
AB 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.