Wang Jinrong, Wang Yin, Long Jianyin, Chang Benny H J, Wilson Mathew H, Overbeek Paul, Danesh Farhad R
Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
Genesis. 2010 Jul;48(7):446-51. doi: 10.1002/dvg.20635.
We report the generation and initial characterization of a mouse line expressing tamoxifen-inducible improved Cre (iCre) recombinase (iCre-ER(T2)) under the regulation of NPHS2 (podocin) gene promoter. The resulting transgenic mouse line was named podocin-iCreER(T2) mice. The efficiency of iCre activity was confirmed by crossing podocin-iCreER(T2) with the ROSA26 reporter mouse. By using the floxed ROSA reporter mice, we found that tamoxifen specifically induced recombination in the kidneys. In the absence of tamoxifen, recombination was undetectable in podocin-iCreER(T2);ROSA26 mice. However, following intraperitoneal injection of tamoxifen, selective recombination was observed in the podocytes of adult animals. We further examined the efficiency of recombination by assessing various tamoxifen exposure regimens in adult mice. These results suggest that podocin-iCre-ER(T2) mouse provides an excellent genetic tool to examine the function of candidate genes in podocytes in a spatially and temporally-restricted manner.
我们报告了在NPHS2（足突蛋白）基因启动子调控下表达他莫昔芬诱导型改良型Cre（iCre）重组酶（iCre-ER(T2)）的小鼠品系的产生及初步特征。所得到的转基因小鼠品系被命名为足突蛋白-iCreER(T2)小鼠。通过将足突蛋白-iCreER(T2)与ROSA26报告基因小鼠杂交，证实了iCre活性的效率。利用携带loxP侧翼序列的ROSA报告基因小鼠，我们发现他莫昔芬能特异性地诱导肾脏中的重组。在没有他莫昔芬的情况下，在足突蛋白-iCreER(T2);ROSA26小鼠中未检测到重组。然而，腹腔注射他莫昔芬后，在成年动物的足细胞中观察到了选择性重组。我们通过评估成年小鼠的各种他莫昔芬暴露方案，进一步检测了重组效率。这些结果表明，足突蛋白-iCre-ER(T2)小鼠提供了一种优秀的遗传工具，可在空间和时间受限的方式下研究足细胞中候选基因的功能。
