Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY. [brain]

Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse brain. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice. To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of brains of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development the nervous system and pathogenesis of neurological diseases in the brain. Total RNAs isolated from the brain of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.