小鼠模型与人类疾病

小鼠是人类疾病理想的动物模型,不仅因为小鼠在生理上与人类极为相似而且小鼠的遗传资源非常丰富,其大量的传变异可作为研究人类的借鉴。另外,高分辨率的小鼠遗传及物理连锁图谱已经建成,小鼠基因组的测序工作不久即将完成,而且维修小鼠基因组的技术（包括建立转基因小鼠,基因敲除,以及改建小鼠染色体的技术）也已具备,分析复杂遗传病的方法也相继建立……。这些进展加速了对小鼠疾病基因位点的鉴定与克隆,同时也促进了新模型的建立,从而使得小鼠成为人类疾病动物模型的首选。小鼠传学分析的技术与资源,将简要介绍用于建立人类疾病的动物模型的基本技术与方法,以及现有的小鼠传资源,在以后各部分中,将列举涉及多种人类疾病的100多个小鼠模型,其中大多数的模型的变异,在小鼠与患者的表型极为相似;因而有助于人们理解人类疾病及寻找有效的预防,治疗方法。

The mouse model and human disease

The mouse is an ideal model organism for studies of human disease, because mouse is physiologically very similar to human. Also, there is a large genetic reservoir of potential models of human diseases that has been generated. In addition, high- resolution genetic and physical linkage maps are now available and the sequence of mouse genome will be completed in the near future. Furthermore, the techniques necessary for the modification of mouse genome, such as transgenic and knockout techniques, and chromosome engineering methods have been established. These techniques enable us to introduce any mutations anywhere in the mouse genome. The methods for analyzing complex genetic diseases also have been developed. These advances facilitate the identification and cloning of mouse disease loci and the establishment of new models. It makes mouse the model organism of choice by academic and industrial researchers to study human diseases. In Part I of this review, we summarize the classical and modern approaches that provide the basis of establishing mouse model of human diseases. In the following parts, we will list more than 100 mouse models of human diseases. In most of these models, the mouse mutant phenotype closely resembles the human disease phenotype. These mouse models are valuable sources for the understanding of the human diseases and they can be used to develop strategies for prevention and treatment of the diseases.