Identification of the diabetogenic gene and its related genes of high fat diet-induced diabetes by using novel mouse model

利用新型小鼠模型鉴定高脂饮食诱发糖尿病的致糖尿病基因及其相关基因

• 批准号: 21380079
• 负责人: HORIO Fumihiko
• 金额: $ 11.98万
• 依托单位: Nagoya University
• 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 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21380079/
• 关键词: 栄養生化学; 糖尿病; 糖尿病遺伝子; 高脂肪食; マウス

SMXA-5 mouse is a novel animal model for type 2 diabetes induced by high fat diet-feeding. We have mapped the diabetic QTL (quantitative trait locus:T2dm2sa) on chromosome 2 of SMXA-5 mouse. The aim of this study is to choose the candidate gene for this diabetogenic gene and identify it as a causative gene. Simultaneously, the controlled genes by the isolated gene, which contribute to the development of diabetes,were screened.The chromosomal region which this diabetogenic gene exists was narrowed to 5Mb region of chromosome 2 by the phenotipic analyses of several diabetic congenic strains. As a candidate gene, Rapgef 4 was chosen. In the exon of Rapgef4 of SMXA-5 mouse, we observed a mutation causing the amino acid substitution. Further study is needed to clarify that this mutation of rapgef4 caused the development of diabetes.

SMXA-5小鼠是一种新型的高脂饮食诱导的2型糖尿病动物模型。本研究定位了SMXA-5小鼠2号染色体上的糖尿病QTL（Quantitative trait locus：T2 dm 2sa）。本研究的目的是选择该基因的候选基因，并确定其为一个致病基因。同时，对分离的基因进行表型分析，筛选出与糖尿病发生有关的基因，并将该基因存在的染色体区域缩小到2号染色体的5 Mb区域。作为候选基因，Rapgef 4被选中。在SMXA-5小鼠的Rapgef 4外显子中，我们观察到一个导致氨基酸替换的突变。需要进一步的研究来阐明rapgef 4的这种突变导致了糖尿病的发展。

项目成果

Establishment of consomic strains derived from A/J and SM/J mice for genetic analysis of complex traits

• DOI: 10.1007/s00335-012-9435-x
• 发表时间: 2012-12-01
• 期刊: MAMMALIAN GENOME
• 影响因子: 2.5
• 作者: Ohno, Tamio;Hata, Keiko;Nishimura, Masahiko
• 通讯作者: Nishimura, Masahiko

SMXA-5マウスが有する脂肪肝感受性遺伝子座(Fllsa)の候補遺伝子の検討

SMXA-5小鼠脂肪肝易感位点（Fllsa）候选基因的检测

• 发表时间: 2011
• 作者: 立石壮志;小林美里;都築佳奈;大野民生;村井篤嗣;堀尾文彦
• 通讯作者: 堀尾文彦

ビタミン総合事典、日本ビタミン学会編集

日本维生素学会编辑的综合维生素百科全书

• 发表时间: 2010
• 作者: 和田濱裕之;岩崎健佑;石本政男;西澤けいと;裏出令子;Y.Nakamura;加藤久典;堀尾文彦(分担執筆)
• 通讯作者: 堀尾文彦(分担執筆)

Coffee and Caffeine Improve Insulin Sensitivity and Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet

• DOI: 10.1271/bbb.110452
• 发表时间: 2011-12-01
• 期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
• 影响因子: 1.6
• 作者: Matsuda, Yuji;Kobayashi, Misato;Horio, Fumihiko
• 通讯作者: Horio, Fumihiko

Genetic analysis of abdominal fat distribution in SM/J and A/Jmice.

SM/J 和 A/J 小鼠腹部脂肪分布的遗传分析。

• 发表时间: 2010
• 期刊: J Lipid Res.
• 作者: Kobayashi M;Ohno T;et al.
• 通讯作者: et al.