Wild type mice (Trsp) vs Trsp-knockout mice (DTrsp) or A34 or G37L or G37H transgenic mice

Comparative analysis of gene expression in the liver of the Trsp-knockout mice (Trspfl/fl-AlbCre+/+) and A34 (Trspfl/fl-AlbCre+/+-A34t/t), G37L (Trspfl/fl-AlbCre+/+-G37t/t; 2 copies), G37H (Trspfl/fl-AlbCre+/+-G37t/t; 16 copies) transgenic mice with gene expression of wild type mice (Trsp+/+-AlbCre+/+). Sec (selenocysteine) is biosynthesized on its tRNA and incorporated into selenium-containing proteins (selenoproteins) as the 21st amino acid residue. Selenoprotein synthesis is dependent on Sec tRNA and the expression of this class of proteins can be modulated by altering Sec tRNA expression. The gene encoding Sec tRNA (Trsp) is a single-copy gene and its targeted removal in liver demonstrated that selenoproteins are essential for proper function wherein their absence leads to necrosis and hepatocellular degeneration. In the present study, we found that the complete loss of selenoproteins in liver was compensated for by an enhanced expression of several phase II response genes and their corresponding gene products. The replacement of selenoprotein synthesis in mice carrying mutant Trsp transgenes, wherein housekeeping, but not stress-related selenoproteins are expressed, led to normal expression of phase II response genes. Thus the present study provides evidence for a functional link between housekeeping selenoproteins and phase II enzymes. Trsp vs DTrsp; Trsp vs A34; Trsp vs G37L; Trsp vs G37H. Biological replicates from littermates. One replicate per array.本研究针对Trsp敲除小鼠（Trspfl/fl-AlbCre+/+）、A34转基因小鼠（Trspfl/fl-AlbCre+/+-A34t/t）、G37L转基因小鼠（Trspfl/fl-AlbCre+/+-G37t/t；2拷贝）及G37H转基因小鼠（Trspfl/fl-AlbCre+/+-G37t/t；16拷贝）的肝脏基因表达开展比较分析，并以野生型小鼠（Trsp+/+-AlbCre+/+）的肝脏基因表达作为对照。硒代半胱氨酸（Sec, selenocysteine）可在其tRNA（转运RNA）上完成生物合成，并作为第21种氨基酸残基掺入含硒蛋白（selenoproteins）中。硒蛋白的合成依赖于Sec tRNA，该类蛋白的表达水平可通过调控Sec tRNA的表达进行调节。编码Sec tRNA的基因（Trsp）为单拷贝基因，在肝脏中特异性敲除该基因的实验证实，硒蛋白对维持肝脏正常功能至关重要，其缺失会引发肝细胞坏死与退行性病变。本研究发现，肝脏中硒蛋白的完全缺失可通过若干II相应答基因及其对应编码产物的表达上调实现代偿。而在携带突变型Trsp转基因、仅表达持家型而非应激相关硒蛋白的小鼠中恢复硒蛋白合成后，II相应答基因的表达可恢复至正常水平。因此本研究为持家型硒蛋白与II相酶之间的功能关联提供了实验证据。本研究的比较分组如下：Trsp组 vs DTrsp组；Trsp组 vs A34组；Trsp组 vs G37L组；Trsp组 vs G37H组。实验重复样本均来自同窝幼崽，每块基因芯片对应一个重复样本。