Polyploid cells in liver and pancreas display enhanced somatic instability of the CTG•CAG repeat. (A, B) Liver hepatocytes from a 17-month-old mouse and pancreatic acinar cells from a 21-month-old mouse were isolated, fixed, stained with propidium iodide and FACS purified based on DNA content. Preparative sorting profiles based on PI fluorescence intensity are shown. All 2n hepatocytes were mononuclear, whereas ~80% cells in the 4n and 8n pools of hepatocytes were binuclear (C, inset; typical examples of cells in the sorted 2n and 4n cell pools stained with Giemsa, are shown). Note that pancreas contained only diploid and tetraploid cells (a fluorescent PAS staining of zymogen inclusions established the identity of acinar cells (D, inset)). (C, D) CTG•CAG length profiles of hepatocytes and acinar cells demonstrated much larger average repeat length and almost complete absence of progenitor alleles in cells with 4n DNA (red; liver hepatocytes and acinar cells) and 8n DNA (black; liver hepatocytes only). In the 2n pools obtained from liver and pancreas (blue) only a small percentage of cells contained expanded repeats. Arrows indicate the position of the progenitor allele determined from analysis of tail DNA at time of weaning.