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

Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse liver. 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 livers 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 of hepatic system and pathogenesis of hepatic system diseases in the liver. Total RNAs isolated from the liver of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.

本研究针对异位表达的人SRY（human SRY，hSRY）对小鼠肝脏基因表达的影响展开分析。我们推测，人SRY基因的异常表达可能会影响转基因小鼠的发育与生理机能。为验证该假说，本研究构建了Cre-LoxP转基因激活系统，从而在单细胞胚胎阶段激活并表达hSRY转基因。此类转基因小鼠出生时体型与非转基因同窝仔鼠无显著差异，但出生后生长迟缓，且全部在出生后两周内死亡。为明确与该表型相关的分子变化，本研究对表达hSRY（hSRY-ON）与不表达hSRY（hSRY-OFF）转基因的仔鼠肝脏转录组进行了分析。结果表明，hSRY的异位表达会改变肝脏中大量与肝脏系统发育及肝脏系统疾病发病机制相关的基因的表达模式，该发现具有重要参考价值。本研究将从出生后第6天（P6）的雄性hSRY-ON小鼠肝脏中提取的总RNA，与同年龄雄性hSRY-OFF小鼠的肝脏总RNA进行了对比分析。