Attie Alan D, Churchill Gary A, Nadeau Joseph H
aDepartment of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin bThe Jackson Laboratory, Bar Harbor, Maine cPacific Northwest Research Institute, Seattle, Washington, USA.
Curr Opin Endocrinol Diabetes Obes. 2017 Apr;24(2):83-91. doi: 10.1097/MED.0000000000000321.
The task of cataloging human genetic variation and its relation to disease is rapidly approaching completion. The new challenge is to discover the function of disease-associated genes and to understand the pathways that lead to human disease. We propose that achieving this new level of understanding will increasingly rely on the use of model organisms. We discuss the advantages of the mouse as a model organism to our understanding of human disease.
The collection of available mouse strains represents as much genetic and phenotypic variation as is found in the human population. However, unlike humans, mice can be subjected to experimental breeding protocols and the availability of tissues allows for a far greater and deeper level of phenotyping. New methods for gene editing make it relatively easy to create mouse models of known human mutations. The distinction between genetic and epigenetic inheritance can be studied in great detail. Various experimental protocols enable the exploration of the role of the microbiome in physiology and disease.
We propose that there will be an interdependence between human and model organism research. Technological advances and new genetic screening platforms in the mouse have greatly improved the path to gene discovery and mechanistic studies of gene function.
编目人类遗传变异及其与疾病的关系这项任务正迅速接近完成。新的挑战是发现与疾病相关基因的功能，并了解导致人类疾病的途径。我们认为，要达到这一新的理解水平将越来越依赖于模式生物的使用。我们讨论了小鼠作为模式生物对于我们理解人类疾病的优势。
现有的小鼠品系所具有的遗传和表型变异与人类群体中发现的一样多。然而，与人类不同的是，小鼠可以进行实验性繁殖方案，并且组织的可获得性使得表型分析的程度更高、更深入。新的基因编辑方法使得创建已知人类突变的小鼠模型相对容易。遗传和表观遗传继承之间的区别可以得到非常详细的研究。各种实验方案能够探索微生物群落在生理学和疾病中的作用。
我们认为人类和模式生物研究之间将存在相互依存关系。小鼠方面的技术进步和新的基因筛选平台极大地改善了基因发现和基因功能机制研究的途径。
