| Behavioral Assessment in Mouse Models of
Huntington’s Disease Reported by Lisa J. Bain.
Abstract:
In preparation for animal testing of compounds that have shown efficacy in in vitro and cell based screens for Huntington’s disease, the Hereditary Disease Foundation (HDF) convened a workshop in Cardiff, Wales to consider the optimal approach for animal testing. Mouse models are needed to test important motor and cognitive dysfunctions that mimic those seen in humans. Several investigators showed videotapes demonstrating the progression of symptoms in mice using a variety of assessments that test motor and cognitive functions. Participants raised concerns about the standardization and reproducibility of these assessments if they are going to be compared across a diverse set of laboratories. Their concerns fell into three general areas: methods, equipment, and background strains of mice. Neuropathologic assessments were also demonstrated and discussed. Concern was raised about standardization of immunostaining reagents. While cognitive testing will be extremely important in the search for treatments, few cognitive assessments have been validated in mice. Work is ongoing in this area. The group also considered whether there is a preferred mouse model in which to test potential therapeutics. The R6/2 mouse develops pathology very early and quickly, allowing more rapid throughput; yet a more slowly developing model might be more representative of the human disease and would allow testing of agents in earlier stages of the disease. At the end of the meeting, a subgroup drew up recommendations for a standard protocol that could be used across many labs to test potential therapies. These recommendations demand further discussion and will be presented at the Boston meeting in August, 2002.
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