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|Title:||HYPERKINETIC AND RIGID GAIT IN R6/2 MICE, A MODEL OF HUNTINGTON’S DISEASE|
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|Authors/Affiliations:||3 Ajit Kale; 2 Scott McCue; 1 Ivo Amende; 3 Thomas Hampton*; |
1 3Caritas St. Elizabeth’s Medical Center, Tufts University, Boston, MA, USA; 2 Mouse Specifics, Inc., USA; 3 The CuraVita Corporation, USA
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|Content:||Objectives: The R6/2 transgenic mouse model is widely studied to understand the pathogenesis of Huntington’s disease [HD] and test therapies. It is not yet clear how the overt chorea, which is a characteristic of disturbed locomotion in HD, will manifest itself in a mouse model. Comprehensive gait analysis has not yet been performed in R6/2 mice. Accordingly, we studied posture and gait in young presymptomatic R6/2 mice.|
Materials and Methods: Ventral plane videography was used to image 3 ~4 week old male R6/2 mice and age-matched wild-type [WT] mice walking 21 cm/s on a transparent treadmill belt. Gait indices were based on ~10 consecutive strides for each mouse.
Results: Gait was hyperkinetic as shown by significantly longer stride length in young R6/2 than in WT mice [6.0 +/- 0.1 cm vs. 5.4 +/- 0.1 cm, P<0.05]. Stride duration was significantly longer [283 +/- 4 ms vs. 256 +/- 2 ms, P<0.05], due to a longer swing duration [102 +/- 3 ms vs. 85 +/- 3 ms, P<0.05] in R6/2 than in WT mice. Gait was more rigid as shown by significantly reduced hind paw area step-to-step variability [5.6 +/- 0.4 % vs. 9.7 +/- 0.7%, P<0.05], reduced hind paw placement angle variability [10.4 +/- 1.6 % vs. 17.0 +/- 2.3 %, P<0.05], and reduced forepaw step angle variability [15.8 +/- 0.6% vs. 29.3 +/- 4.7%, P<0.05].
Conclusion: The young R6/2 mice demonstrated disturbed locomotion and impaired motor coordination, as shown by the hyperkinetic and rigid gait. Our findings are indicative of a rodent’s manifestation of chorea characteristics in patients with HD. The R6/2 mouse model provides an opportunity to search for early presymptomatic phenotypes or biomarkers of Huntington’s disease.
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