Genetic analyses of the susceptibility gene for streptozotocin induced diabetes in A/J mice

2014 Fiscal Year Final Research Report

• Project/Area Number: 23500494
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory animal science
• Research Institution: Nagoya University
• Principal Investigator: OHNO Tamio 名古屋大学, 医学(系)研究科(研究院), 准教授 (90293620)
• Co-Investigator(Renkei-kenkyūsha): HORIO Fumihiko 名古屋大学, 生命農学研究科, 教授 (20165591) ; IKEGAMI Hiroshi 近畿大学, 医学部, 教授 (20221062)
• Research Collaborator: MAEGAWA Tomoki 名古屋大学, 大学院医学系研究科
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: マウス / 体系的遺伝解析系 / コンソミック系統 / コンジェニック系統 / ストレプトゾトシン / 糖尿病感受性遺伝子

Outline of Final Research Achievements

Streptozotocin (STZ) is a well-known diabetogenic agent that has cytotoxic activities in pancreatic B-cells. It has been reported that inbred mouse strains differ in their susceptibility to the diabetogenic effect of STZ treatment. However, there has been little use of forward genetic approaches to analyze STZ susceptibility. Our analysis using A/J, SM/J and A/J-11SM mice identified the diabetogenic gene to STZ on Chr. 11. We developed Chr. 11 congenic strains from A/J-11SM mice and measured their susceptibility to STZ. Congenic mapping indicated that major locus for STZ susceptibility was present between D11Mit163 (27.7Mb) to D11Mit51 (36.4Mb) on Chr. 11. Exome sequencing analysis in SM/J and A/J mice revealed a non-synonymous coding mutation (A132S) in the Mpg (N-methylpurine-DNA glycosylase) gene suggested this to be the causative gene for STZ susceptibility in the A/J mouse strain.

Free Research Field

実験動物学