Elevated levels of mosaic aneuploidy in brain cells and fibroblast cell lines from human Huntington’s disease donors and in brain cells from Huntington’s disease mouse models

Background Huntington’s disease (HD) is a progressive neurodegenerative disorder that presents with motor and cognitive deficits psychiatric disturbances. HD associated autosomal dominant inheritance of CAG trinucleotide repeat expansion mutation in the huntingtin (HTT) gene. The protein localizes to spindle poles required for proper mitotic orientation, chromosome segregation, cell cycle regulation. mature mutant has an expanded polyglutamine region (>35 repeats) near its N terminus, which leads neuronal dysfunction death. Mouse models exhibit defects microtubule function Studies from our laboratory others have shown elevated levels aneuploidy many disorders characterized by deficits, including Alzheimer’s frontotemporal lobar degeneration. Here, we investigated whether segregation lead mosaic consequent apoptosis may also contribute loss HD. Methods Single-cell suspensions cortex cerebellum human donors were analyzed using FISH 21, NeuN immunostaining, and/or TUNEL staining. Fibroblast lines FISH. mouse chromosomes 5 16. Cell arrest, defects, ploidy, profiles fibroblast are being flow cytometry immunofluorescence microscopy. Results Increased observed brain cells compared age-matched healthy control donors. mice wild-type mice. ongoing studies will be presented. Conclusions Taken together results previous studies, these data provide evidence genomic instability serve as shared mechanism underlying disorders. Our findings highlight need further investigate biological mechanism(s) pathology set stage novel therapeutic approaches applied other