Izpisua Belmonte Juan Carlos, Callaway Edward M, Caddick Sarah J, Churchland Patricia, Feng Guoping, Homanics Gregg E, Lee Kuo-Fen, Leopold David A, Miller Cory T, Mitchell Jude F, Mitalipov Shoukhrat, Moutri Alysson R, Movshon J Anthony, Okano Hideyuki, Reynolds John H, Ringach Dario, Sejnowski Terrence J, Silva Afonso C, Strick Peter L, Wu Jun, Zhang Feng
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Systems Neurobiology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuron. 2015 May 6;86(3):617-31. doi: 10.1016/j.neuron.2015.03.021.
One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators, and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive, and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward.
小鼠模型的一大优势在于已开发出的大量遗传工具。显著的例子包括基因组定向修饰方法,以及基因的调控表达或失活方法。在神经科学领域,目前在小鼠特定神经元类型中表达报告基因、神经元活动指标和视蛋白已成为常规操作。然而,小鼠和人类在解剖学、生理学、认知和行为方面存在相当大的差异,在某些研究领域,这限制了从小鼠获得的见解应用于理解人类神经生物学的程度。最近的几项进展现已使将这些工具应用于理解灵长类大脑的目标触手可及。在这里,我们描述这些进展,考虑它们在推进我们对人类大脑和脑部疾病理解方面的潜力,讨论生物伦理考量,并描述未来前进所需的条件。