Bradley Cara K, Takano Elena A, Göthert Joachim R, Göttgens Berthold, Green Anthony R, Begley C Glenn, van Eekelen J Anke M
Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Subiaco, Western Australia, Australia.
Genesis. 2007 Mar;45(3):145-51. doi: 10.1002/dvg.20274.
The Cre/LoxP system provides a powerful tool to investigate gene function in vivo. This system requires Cre-recombinase expressing mouse lines that permit control of gene recombination in a tissue-specific and time-dependent manner. To allow spatio-temporal gene deletion in specific central nervous system (CNS) neuronal populations, we generated mice with a tamoxifen-inducible Cre (Cre-ER(T)) transgene under control of the Scl/Tal1 neural promoter/enhancer -0.9E3 (-0.9E3CreER(T) transgenic mice). Using Cre-reporter mice we have shown that tamoxifen-mediated Cre-ER(T) recombination in -0.9E3CreER(T) mice recapitulated the anticipated expression pattern of Scl in the caudal thalamus, midbrain, hindbrain, and spinal cord. Cre-mediated recombination was also effectively induced during embryogenesis and marked the same population of neurons as observed in the adult. Additionally, we identified a tamoxifen-independent constitutively active -0.9E3CreER(T) mouse line that will be useful for gene deletion during early neurogenesis. These -0.9E3CreER(T) mice will provide tools to investigate the role of neuronal genes in the developing and mature CNS. CNS.
Cre/LoxP系统为在体内研究基因功能提供了一个强大的工具。该系统需要表达Cre重组酶的小鼠品系，以便以组织特异性和时间依赖性的方式控制基因重组。为了在特定的中枢神经系统（CNS）神经元群体中实现时空基因缺失，我们构建了在Scl/Tal1神经启动子/增强子-0.9E3（-0.9E3CreER(T)转基因小鼠）控制下带有他莫昔芬诱导型Cre（Cre-ER(T)）转基因的小鼠。使用Cre报告基因小鼠，我们发现他莫昔芬介导的-0.9E3CreER(T)小鼠中的Cre-ER(T)重组重现了Scl在丘脑尾部、中脑、后脑和脊髓中的预期表达模式。Cre介导的重组在胚胎发育期间也能有效诱导，并且标记的神经元群体与成年小鼠中观察到的相同。此外，我们鉴定出一种不依赖他莫昔芬的组成型活性-0.9E3CreER(T)小鼠品系，它将有助于在早期神经发生过程中进行基因缺失。这些-0.9E3CreER(T)小鼠将为研究神经元基因在发育中和成熟的中枢神经系统中的作用提供工具。中枢神经系统。
