Gawlik Alexander, Quaggin Susan E
The Samuel Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, ON, Canada.
Curr Mol Med. 2005 Aug;5(5):527-36. doi: 10.2174/1566524054553522.
Complete mapping of the genome in a number of organisms provides a challenge for experimental nephrologists to identify potential functions of a vast number of new genes in the kidney. Since knockout technologies have evolved in the early eighties the mouse has become a valuable model organism. Researchers can now artificially eliminate the expression of specific genes in a mammalian organism and examine the phenotype. New developments have emerged that allow investigators to knock out a gene specifically in the kidney. Several kidney-specific promoters provide valuable tools and bacterial artificial chromosome (BAC) based techniques like recombineering will enhance both number and accuracy of new mouse lines with spatially controlled gene expression. In addition to spatial control, tetracycline- or tamoxifen-inducible systems, provide the possibility of influencing the temporal expression pattern of a gene enabling researchers to dissect its functions in adult organisms. Knocking out a gene will continue to be the gold standard for defining the role of a specific gene whereas tissue-specific gene knockdown using RNA interference represents an alternative approach for generating lower-priced and fast loss of function models. In addition to reverse genetic approaches, forward genetic techniques like random mutagenesis in mice continue to evolve and will enhance our understanding of disease mechanisms in the kidney.
对许多生物体的基因组进行完整测序，给实验肾脏病学家带来了挑战，即要确定肾脏中大量新基因的潜在功能。自上世纪八十年代初基因敲除技术发展以来，小鼠已成为一种有价值的模式生物。研究人员现在可以在哺乳动物体内人工消除特定基因的表达并检查其表型。新的进展已经出现，使研究人员能够在肾脏中特异性敲除基因。几种肾脏特异性启动子提供了有价值的工具，基于细菌人工染色体（BAC）的技术，如重组工程，将提高具有空间控制基因表达的新小鼠品系的数量和准确性。除了空间控制外，四环素或他莫昔芬诱导系统提供了影响基因时间表达模式的可能性，使研究人员能够剖析其在成年生物体中的功能。敲除基因仍将是定义特定基因作用的金标准，而使用RNA干扰进行组织特异性基因敲低是生成低成本、快速功能丧失模型的另一种方法。除了反向遗传学方法外，小鼠随机诱变等正向遗传学技术也在不断发展，将增进我们对肾脏疾病机制的理解。
