Lunardi Andrea, Nardella Caterina, Clohessy John G, Pandolfi Pier Paolo
Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
Cold Spring Harb Protoc. 2014 Jan 1;2014(1):17-31. doi: 10.1101/pdb.top069757.
The extraordinary endeavor to faithfully model human disorders in mice began in the early 1900s, and in the century since has delivered fundamental advances in our understanding and treatment of human disease. Although it could not be appreciated at the time, 99% of mouse protein-coding genes have an equivalent homolog in the human genome, despite the striking differences in appearance between mouse and man. This remarkable genetic similarity, together with our ability to finely engineer the murine genome, has made the mouse the ideal animal in which to model and analyze human biology and disease. Here we describe this remarkable shared journey between human and mouse, and envisage the next generation of mouse models, which will no doubt prove increasingly sophisticated and even more faithful to human disease. We also address the strategic use of mice in the fight against cancer, and the role they will play in the development of therapies to eradicate this disease.
在小鼠身上忠实地模拟人类疾病的非凡努力始于20世纪初,自那以后的一个世纪里,我们对人类疾病的理解和治疗取得了根本性的进展。尽管当时还无法认识到,但尽管小鼠和人类在外观上存在显著差异,99%的小鼠蛋白质编码基因在人类基因组中都有对应的同源基因。这种显著的遗传相似性,加上我们精细改造小鼠基因组的能力,使小鼠成为模拟和分析人类生物学及疾病的理想动物。在这里,我们描述了人类和小鼠之间这段非凡的共同历程,并展望了下一代小鼠模型,毫无疑问,它们将越来越复杂,甚至更忠实地模拟人类疾病。我们还讨论了在抗癌斗争中对小鼠的战略利用,以及它们在开发根除这种疾病的疗法中所起的作用。