Development of murine models of disease using a novel non-obese type 2 diabetes mellitus mouse discovered in Japan and isolation of responsible genes

使用日本发现的新型非肥胖 2 型糖尿病小鼠开发疾病小鼠模型并分离相关基因

基本信息

批准号：
21300156
负责人：
松島芳文
金额：
$ 10.65万
依托单位：
Research Institute for Clinical Oncology, Saitama Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2012
项目状态：
已结题

项目摘要

The murine models of diabetes reported in the present study are novel models of spontaneous disease. The mice are non-obese and show autosomal dominant inheritance. The type 2 diabetes models are heterozygote strains, whereas the neonatal diabetes mellitus models are homozygote strains that die due to severe hyperglycemia at 4 days after birth. The progenitor mutant mouse was discovered in the F2 population between the two inbred mouse strains NC/Jic and KOR1. Because diabetes is a multifactorial disease and its genetic analysis is difficult, murine models with the same genetic background were developed to isolate modification genes responsible for the onset of diabetes. Hybridization was used to introduce the mutant genes into 10 inbred strains with different genetic backgrounds to create congenic murine models of diabetes and into four apoE-deficient hyperlipidemia mouse (SHL) strains to develop murine models of diabetes with hyperlipidemia. Development of 機関番号：82402 研究種目：基盤研究(B) 研究期 … More 間：2009年度～2012年度課題番号：21300156 研究課題名（和文）我国で発見された新規非肥２型糖尿病マウスによる疾患モデル群樹立と原因遺伝子の特定研究課題名（英文） Development of murine models of disease using a novel non-obese type 2 diabetes mellitus mouse discovered in Japan and isolation of responsible genes 研究代表者松島芳文（マツシマヨシブミ）研究者番号：10094955 congenic murine models is completed at the N12 or a later generation. Eight congenic strains for diabetes (AKR, BALB/c, C3H/He, C57BL/6, DBA/2, JF1, NC/Jic, and NC/Nga) and four strains for diabetes with hyperlipidemia (B6.SHL, C.SHL, C3.SHL, and D2.SHL) have been successfully developed in this study. However, A/J and KORI are both at the N6 generation and are being advanced to the later generations to generate congenic strains. These congenic strains showed prominent differences with respect to various phenotypic characteristics, such as age in weeks at urinary sugar manifestation, blood sugar level, and sex difference, at disease onset. Therefore, they also have utility as novel models for personalized medicine. There are, as yet, few reports on the development of diabetic nephropathy models that researchers long for. However, pathological observations of the kidneys of the C57BL/6 congenic strain suggest that it may be a novel model of diabetic nephropathy. Positional cloning of the responsible gene has narrowed down the candidate region to the vicinity of the centromere of the mouse chromosome 8. DNA sequencing is ongoing, and the results there of will be available before manuscript submission. Less

在自发疾病的预设研究中，糖尿病的鼠模型是非肥胖的常染色体domil磨损。出生后的4天。修饰基因是代表的发作。：2009年-FY2012信号名称：21300156句子）在日本开发疾病模型的发展和新的非新闻，以及使用一种新型的非肥胖2型糖尿病的疾病模型开发疾病模型的原因（英语句子）。在日本和负责任的基因研究代表Matsu Yoshifumi Shima（Matsushima Yoshibumi）研究人员编号：10094955先驱模型在N12或HE，HE，HE，HE，C57BL/6，DBA/2，DBA/2，JF1，JF1，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC，NC/JIC和NC/NGA）和四个高脂血症的菌株（B6.SHL，C.SHL，C3.SHL和D2.SHL）在S研究中已成功地发展了A/J和Kori。几代人会产生对各种表型特征的先天性菌株，例如尿糖表现，血糖水平和性别差异的年龄但是，研究人员持续的肾病模型的发展。小鼠染色体8的中心