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.
Smith
Donna L
DL
Department of Medical and Molecular Genetics, GKT School of Medicine, King's College, Guy's Hospital, London, UK.
Bates
Gillian P
GP
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006816:Huntington Disease / Q000235:genetics*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction
D017931:DNA Primers