Evaluating Striatal Function in a Murine HD Model Murine genetic models have been developed for Huntington's disease (HD). Appropriate behavioral evaluations are crucial for preclinical evaluation of treatments proposed for humans. Behavioral evaluation in these murine models has been limited largely to assessment of motor function or use of learned behaviors that largely preclude serial evaluations in the same animals. Available data indicates that the most genetically accurate models, so-called 'knockin' models, exhibit pathology relatively restricted to the striatum. Presently used behavioral measures do not assess striatal function specifically. We hypothesize that behavioral measures assessing known striatal functions will be more sensitive measures of behavioral abnormalities in an HD knockin model than previously used behavioral measures. We have chosen two behaviors regulated normally by the striatum, control of grooming sequences and egocentric spatial memory that can be assessed serially in the same animals by simple behavioral methods. We compare assessment of grooming sequences and egocentric spatial memory function with conventional behavioral methods in HD knockin and control littermate mice. We predict that our chosen novel methods will prove more efficient at identifying phenotypic abnormalities than conventional behavioral methods. Validation of these methods will provide new and useful behavioral tools for evaluating murine disease models. ? ? ?
| Tallaksen-Greene, Sara J; Janiszewska, Anita; Benton, Kasha et al. (2010) Lack of efficacy of NMDA receptor-NR2B selective antagonists in the R6/2 model of Huntington disease. Exp Neurol 225:402-7 |
