Murine trisomy 16 model of Down's syndrome: Central nervous system electron microscopic observations

Abstract

Murine trisomy 16 is an excellent model for the human Down's syndrome (DS) (13). Electron microscopic (EM) observations were made of the cortical plate within the developing telencephalic vesicle at the gestational age of E17. The EM observations revealed: (A) microtubular profiles which were more coiled and curved in the trisomie condition; (B) poor cell-to-cell apposition and increased cellular membrane fragmentation in trisomy 16; (C) increased nuclear contour irregularity in trisomic neurons; (D) significant decrease in the cross-sectional area of neuronal nuclei in trisomy 16 ( p<0.01). The microtubular observations lend credence to the hypothesis that abnormal cytoskeletal interactions may underlie the mental deficiency seen in DS and may predis- pose to the eventual development of Alzheimer's disease (AD) in DS individuals (39,40). The cellular membrane findings may be related to reported CNS membrane lipid abnormalities in DS (1,2). The nuclear morphologic observations may be related to the reported differences in chromatin and nuclear histone expression in AD (7,8). These results strengthen the role of the trisomy 16 mouse as a model for DS and potentially for AD.