Monitoring aggregate formation in organotypic slice cultures from transgenic mice

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the first exon of the HD gene. It encodes a protein known as huntingtin, which aggregates in the nuclei of affected neurons. These aggregates are an obvious therapeutic target, thus an organotypic slice culture assay has been designed to screen potential antiaggregation compounds using the R6/2 mouse model of HD. This assay allows the aggregates to be fully quantified using fluorescent confocal microscopy and gives additional information perturbing to drug solubility, delivery, toxicity, concentration, and efficacy of inhibitors. This information is essential to the planning and application of an in vivo drug trial in the R6/2 mice.