Zhang Hongjie, Fujitani Yoshio, Wright Christopher V E, Gannon Maureen
Department of Medicine, Vanderbilt University, Nashville, TN 37232-6303, USA.
Genesis. 2005 Jul;42(3):210-7. doi: 10.1002/gene.20137.
We generated pdx1(PB)CreERtrade mark transgenic mice in which a pancreatic endocrine-specific enhancer (pdx1(PB)) drives expression of a tamoxifen (TM)-inducible Cre recombinase/estrogen receptor fusion protein. We previously showed that this enhancer directs expression to immature endocrine cells as well as postnatal islets. This transgene provides spatial and temporal control of gene inactivation in pancreatic islets. Three transgenic lines were generated and crossed with R26R mice to assess recombination efficiency. TM-dependent lacZ expression was observed in islets from all three lines. One line was chosen for further study based on its strong islet-specific recombination in embryos and adults. In this line, a dose-dependent increase in recombination efficiency was observed in endocrine cells. Our data suggest that this transgenic line will be a valuable tool to inactivate genes in pancreatic endocrine cells during development or in the adult. The dose-dependent nature of recombination suggests a potential use for this line in the generation of genetic mosaic animals.
我们构建了pdx1(PB)CreER™转基因小鼠,其中胰腺内分泌特异性增强子(pdx1(PB))驱动他莫昔芬(TM)诱导型Cre重组酶/雌激素受体融合蛋白的表达。我们之前表明,该增强子可将表达导向未成熟内分泌细胞以及出生后的胰岛。该转基因可在空间和时间上控制胰岛中的基因失活。构建了三个转基因品系,并与R26R小鼠杂交以评估重组效率。在所有三个品系的胰岛中均观察到了TM依赖性lacZ表达。基于其在胚胎和成年小鼠中强烈的胰岛特异性重组,选择了一个品系进行进一步研究。在该品系中,在内分泌细胞中观察到重组效率呈剂量依赖性增加。我们的数据表明,该转基因品系将是在发育过程中或成年期使胰腺内分泌细胞中的基因失活的有价值工具。重组的剂量依赖性性质表明该品系在生成遗传镶嵌动物方面具有潜在用途。