利用遗传多样性小鼠资源筛选CA16致病相关基因

Screening of CA16 pathogenicity-related genes using Genetic Diversity Mice

目的柯萨奇病毒A16型(Coxsachievirus A16,CA16)是手足口病主要致病病原体之一,其致病机制尚未明确。本研究利用遗传多样性小鼠(Genetic Diversity Mice)筛选CA16致病相关基因,深入研究该病毒的致病机制。方法选取23个遗传多样性小鼠品系为实验组,近交系C57BL/6小鼠为阴性对照组,均经腹腔感染107 Copies CA16病毒,取材血液和后肢骨骼肌样本,利用实时荧光定量PCR测定样本的病毒载量,之后利用The Gene Mine系统遗传学数据库分析感染数据,筛选获得CA16致病相关基因。结果依据感染小鼠血液和肌肉中病毒拷贝数均高于104 Copies/(μL/mg)的筛选标准,得到7个对CA16易感的遗传多样性小鼠品系,且这些小鼠的骨骼肌组织表现出显著的病理损伤;同时基于The Gene Mine专业数据库的相应数据分析,发现小鼠3号及4号染色体与CA16致病最为相关,并最终筛选到16个可能与CA16致病相关的基因。结论遗传多样性小鼠资源为CA16致病相关基因研究提供新思路。

Objective Coxsackievirus A16(CA16)is the main pathogenic pathogen of hand,foot and mouth disease(HFMD),but its pathogenic mechanism remains unclear.In this study,Genetic Diversity Mice were used to screen the pathogenic genes of CA16 and to explore the pathogenic mechanism.Methods Twenty-three strains of Genetic Diversity Mice were selected as the experimental group and C57BL/6 mice were used as the control group.Both groups were challenged with 10 copies of CA16 by intraperitoneal injection.Blood and hind limb skeletal muscle were collected,and the viral load was detected by real-time quantitative PCR.Then,the GeneMine systems genetics database was used to analyze data of infection and to screen CA16 pathogenicity-related genes.Results Seven mouse strains and 16 genes associated with CA16 were screened from the infection data of Genetic Diversity Mice.For all seven Genetic Diversity Mice strains,the viral loads in blood and muscles tissue were all>10 Copie/(μL/mg)and skeletal muscle showed significant pathological damage.Based on The GeneMine database,the pathogenicity-related genes were mainly distributed in chromosomes 3 and 4.Conclusions Genetic Diversity Mice resources provide a new method for the study of CA16 pathogenicity-related genes.