The analysis of new mouse model for glomerulonephritis and an approach for Th1/Th2 cell regulation by transcription factors

Flsky skin （fsn）小鼠出现肾小球肾炎、牛皮癣、血清IgE高水平和严重贫血。银屑病已知为Th1表型，高水平IgE为Th2表型。转录因子T-bet和GATA-3被认为是Th1/Th2分化的关键调控因子。本研究制备T-bet过表达fsn小鼠（T-bet fsn小鼠）和gta -3过表达fsn小鼠（gta -3 fsn小鼠），与fsn小鼠分析肾小球肾炎及Th1/Th2亚群。结果表明：1。fsn小鼠出现CD4/CD8失衡。fsn小鼠胸腺CD4+CD8+ T细胞数量明显低于野生小鼠。2. T-bet fsn小鼠的蛋白尿比fsn小鼠减少。提示转录调控可能影响fsn小鼠肾小球肾炎的发生。3. fsn小鼠免疫球蛋白亚群分析显示Th2显性背景。4. 在免疫球蛋白亚群分析中，T-bet fsn小鼠显示Th1显性背景。T-bet fsn小鼠血清IgG1水平和IgG2a/IgG1比值低于fsn小鼠。5. 与fsn小鼠相比，T-bet fsn小鼠的存活率没有延长。T-bet fsn小鼠、GATA-3 fsn小鼠和fsn小鼠均在25周内死亡。结果表明，T-bet在fsn小鼠中过表达可改善肾小球肾炎，但不能提高生存率。这些数据表明，Th1/Th2背景可能不是fsn小鼠死亡的原因。fsn小鼠的死亡原因可能是其他原因，比如严重贫血。

Flsky skin (fsn) mice develop glomerulonephritis, psoriasis, a high level of serum IgE, and severe anemia. Psoriasis is known to Th1 phenotype and a high level of IgE is Th2 phenotype. The transcription factors T-bet and GATA-3 are thought to be key regulators of Th1/Th2 differentiation. In this study, T-bet overexpressed fsn mice (T-bet fsn mice) and GATA-3 overexpressed fsn mice (GATA-3 fsn mice) were generated and analyzed with fsn mice about glomerulonephritis and Th1/Th2 subset. The results showing as following : 1. fsn mice showed CD4/CD8 imbalance. Thymus CD4+CD8+ T cells population in fsn mice was decreased than that of wild mice. 2. The proteinuria of T-bet fsn mice decreased than that of fsn mice. The results suggested that transcriptional regulation might effect the development of glomerulonephritis in fsn mice. 3. fsn mice showed Th2 dominant background in immunoglobulin subset analysis. 4. T-bet fsn mice showed Th1 dominant background in immunoglobulin subset analysis. The serum IgG1 level and IgG2a/IgG1 ratio of T-bet fsn mice was lower than those of fsn mice. 5. T-bet fsn mice did not prolong the survival rate than that of fsn mice. T-bet fsn mice, GATA-3 fsn mice, and fsn mice all died within 25 week-old. The results showed that T-bet overexpressed in fsn mice might improve glomerulonephritis, but not survival rate. The data suggested that Th1/Th2 background might not contribute the cause of death in fsn mice. The cause of death in fsn mice might be due to other reasons, such as severe anemia.