Inoue Shuji, Inoue Miki, Fujimura Sayoko, Nishinakamura Ryuichi
Department of Kidney Development, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan.
Genesis. 2010 Mar;48(3):207-12. doi: 10.1002/dvg.20603.
Sall1 is expressed in the metanephric mesenchyme in the developing kidney, and mice deficient in Sall1 show kidney agenesis or dysgenesis. Sall1 is also expressed elsewhere, including in the limb buds, anus, heart, and central nervous system. Dominant-negative mutations of Sall1 in mice and humans lead to developmental defects in these organs. Here, we generated a mouse line expressing tamoxifen-inducible Cre recombinase (CreER(T2)) under the control of the endogenous Sall1 promoter. Upon tamoxifen treatment, these mice showed genomic recombination in the tissues where endogenous Sall1 is expressed. When CreER(T2) mice were crossed with the floxed Sall1 allele, tamoxifen administration during gestation led to a significant decrease in Sall1 expression and small kidneys at birth, suggesting that Sall1 functions were disrupted. Furthermore, Sall1 expression in the kidney was significantly reduced by neonatal tamoxifen treatment. The Sall1CreER(T2) mouse is a valuable tool for in vivo time-dependent and region-specific knockout and overexpression studies.
Sall1在发育中的肾脏的后肾间充质中表达，缺乏Sall1的小鼠表现出肾缺如或发育不全。Sall1也在其他部位表达，包括肢芽、肛门、心脏和中枢神经系统。小鼠和人类中Sall1的显性负性突变会导致这些器官的发育缺陷。在这里，我们构建了一个在Sall1内源性启动子控制下表达他莫昔芬诱导型Cre重组酶（CreER(T2)）的小鼠品系。给予他莫昔芬后，这些小鼠在内源性Sall1表达的组织中出现了基因组重组。当CreER(T2)小鼠与携带floxed Sall1等位基因的小鼠杂交时，在妊娠期给予他莫昔芬会导致出生时Sall1表达显著降低且肾脏较小，这表明Sall1的功能受到了破坏。此外，新生小鼠给予他莫昔芬治疗后，肾脏中的Sall1表达显著降低。Sall1CreER(T2)小鼠是用于体内时间依赖性和区域特异性基因敲除及过表达研究的宝贵工具。
