Lengeling A, Pfeffer K, Balling R
GSF-Research Center for Health and Environment, Institute of Experimental Genetics, Neuherberg, Germany.
Mamm Genome. 2001 Apr;12(4):261-71. doi: 10.1007/s003350040001.
Genetic factors strongly determine the outcome of infectious diseases caused by various pathogens. The molecular mechanisms of resistance and susceptibility in humans, however, remains largely unknown. Complex interactions of multiple genes that control the host response to a pathogen further complicate the picture. Animal models have a tremendous potential to dissect the complex genetic system of host-pathogen interaction into single components. This is particularly true for the mouse, which will continue to develop into an invaluable tool in the identification and cloning of host resistance genes. Three main approaches have been taken to establish mouse models for human infectious diseases: 1) Production of mouse mutants by gene targeting; 2) positional cloning of host-resistance genes in mutant mice; and 3) mapping and characterization of quantitative trait loci (QTL) controlling the complex aspects of host-pathogen interactions. The contribution of all three methods to the understanding of infectious diseases in humans will be reviewed in this work, with a special emphasis on the studies of resistance/susceptibility mechanism in bacterial infections.
遗传因素在很大程度上决定了由各种病原体引起的传染病的结果。然而，人类中抵抗和易感性的分子机制在很大程度上仍然未知。控制宿主对病原体反应的多个基因之间复杂的相互作用使情况更加复杂。动物模型具有巨大的潜力，可将宿主-病原体相互作用的复杂遗传系统分解为单个组成部分。对于小鼠来说尤其如此，它将继续发展成为鉴定和克隆宿主抗性基因的宝贵工具。建立人类传染病小鼠模型主要采用了三种方法：1）通过基因靶向产生小鼠突变体；2）在突变小鼠中对宿主抗性基因进行定位克隆；3）对控制宿主-病原体相互作用复杂方面的数量性状基因座（QTL）进行定位和表征。本文将综述这三种方法对理解人类传染病的贡献，特别强调对细菌感染中抗性/易感性机制的研究。
