The mouse brain transcriptome by SAGE: Differences in gene expression between P30 brains of the partial trisomy 16 mouse model of Down syndrome (Ts65Dn) and normals

Trisomy 21, or Down syndrome (DS) is the most common genetic cause of menta l retardation. Changes in the neuropathology, neurochemistry, neurophysiolo gy, and neuropharmacology of DS patients' brains indicate that there is pro bably abnormal development and maintenance of central nervous system struct ure and function. The segmental trisomy mouse (Ts65Dn) is a model of DS tha t shows analogous neurobehavioral defects. We have studied the global gene expression profiles of normal and Ts65Dn male and normal female mice brains (P30) using the serial analysis of gene expression [SAGE] technique. From the combined sample we collected a total of 152,791 RNA tags and observed 4 5,856 unique tags in the mouse brain transcriptome. There are 14 ribosomal protein genes (nine underexpressed) among the 330 statistically significant differences between normal male and Ts65Dn male brains, which possibly imp lies abnormal ribosomal biogenesis in the development and maintenance of DS phenotypes. This study contributes to the establishment of a mouse brain t ranscriptome and provides the first overall analysis of the differences in gene expression in aneuploid versus normal mammalian brain cells.