Mapping of susceptibility genes to diabetes by high fat diet following QTL analysis of diabetic db mice

糖尿病 db 小鼠 QTL 分析后高脂饮食对糖尿病的易感基因定位

基本信息

  • 批准号:
    17590936
  • 负责人:
  • 金额:
    $ 2.24万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

To identify the susceptibility genes to type 2 diabetes (T2D), we previously identified 2 quantitative trait loci (QTL), which affect body weight, fat pad weight, and fasting blood glucose concentrations in a leptin receptor deficient obese F2 intercross derived from BKS and DBA2 (D2) mice. We also generated congenic mice by repeatingly backcrossing donor (db) mice to recipient D2 mice carrying a given QTL-containing genomic region to test the effect of each QTL on diabetic phenotypes. Introgression of two QTL regions of D2 into BKS background replicated the increase in body weight and fat pad weight. The effect of QTL was dependent on obesity associated with the db/db-induced diabetes. To identify the factors promoting obesity-induced T2D, we conducted genetic studies on two lines of wild type congenic mice (without db loci) with high fat diet. Our findings are as follows ; 1) We found the suitable high fat diet to promote obesity-induced T2D in males and females. 2) We generated congenic mice without db loci by repeatingly backcrossing donor (db) mice to recipient D2 mice. Effects of genomic region were tested by comparing congenic mice having one region from D2 with having BKS alleles. Differences in phenotypes were replicated in body weight and fat pad weight in one line of congenic mice. 3) In another a line, we could not map the locus correlating obesity-induced T2D. 4) In the first line, analyses of six sub-lines identified the target region of eight Mb, which affects body weight induced by high fat diet. Our identification provides insight of obesity-induced type 2 diabetes mellitus.
为了鉴定2型糖尿病(T2 D)的易感基因,我们先前鉴定了2个数量性状位点(QTL),它们影响来自BKS和DBA 2(D2)小鼠的瘦素受体缺陷型肥胖F2杂交小鼠的体重、脂肪垫重量和空腹血糖浓度。我们还通过将供体(db)小鼠与携带给定的含有QTL的基因组区域的受体D2小鼠重复回交来产生同源小鼠,以测试每个QTL对糖尿病表型的影响。将D2的两个QTL区域渗入BKS背景中,重复了体重和脂肪垫重量的增加。QTL的作用依赖于与db/db诱导的糖尿病相关的肥胖。为了确定促进肥胖诱导的T2 D的因素,我们对两种具有高脂肪饮食的野生型同源小鼠(没有db基因座)进行了遗传研究。我们的研究结果如下:1)我们找到了合适的高脂肪饮食,以促进肥胖诱导的T2 D的男性和女性。2)我们通过重复回交供体(db)小鼠与受体D2小鼠产生没有db基因座的同源小鼠。通过比较具有来自D2的一个区域的同类小鼠与具有BKS等位基因的同类小鼠来测试基因组区域的影响。表型的差异复制在体重和脂肪垫重量在一个系的同类小鼠。3)在另一个a系中,我们无法绘制与肥胖诱导的T2 D相关的基因座。4)在第一行中,对六个亚行的分析鉴定了8 Mb的靶区域,其影响由高脂肪饮食诱导的体重。我们的鉴定提供了对肥胖引起的2型糖尿病的认识。

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hypoplasia of endocrine and exocrine pancreas in homozygous transgenic TGF-betal.
纯合转基因 TGF-β 中内分泌和外分泌胰腺发育不全。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hayakawa T;et al.;Hiroshi Yaguchi;Takeshita Y et al.;Hiroshi Yaguchi;Sakurai M et al.;Maki Moritani
  • 通讯作者:
    Maki Moritani
Effect of +36T>C in intron 1 on the glutamine : fructose-6-phosphate amidotransferase 1 gene and its contribution to type 2 diabetes in different populations.
内含子1中36T>C对谷氨酰胺:6-磷酸果糖酰胺转移酶1基因的影响及其对不同人群2型糖尿病的贡献。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Misu H;et al.;Kiyoshi Kunika
  • 通讯作者:
    Kiyoshi Kunika
Genetic association between the PRKCH gene encoding protein kinase Ceta isozyme and rheumatoid arthritis in the Japanese population
日本人群中编码蛋白激酶 Ceta 同工酶的 PRKCH 基因与类风湿性关节炎之间的遗传关联
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    田仲 和宏;他(分担執筆);Shunji Nakano;Nakano S.et al.;Yoichiro Takata;Yoichiro Takata;Keisuke Yagi;Takata Y.et al.;Takata Y.et al.;Yagi K.et al.;Suzue N.et al.;Yoichiro Takata
  • 通讯作者:
    Yoichiro Takata
Identification of candidate genes in type 2 diabetes modifier locus using expression QTL.
使用表达 QTL 鉴定 2 型糖尿病修饰基因座中的候选基因。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hayakawa T;et al.;Hiroshi Yaguchi
  • 通讯作者:
    Hiroshi Yaguchi
Genetic association of single nucleotide polymorphisms in endonuclease G-like 1 gene with type 2 diabetes in a Japanese population
  • DOI:
    10.1007/s00125-007-0631-2
  • 发表时间:
    2007-06-01
  • 期刊:
  • 影响因子:
    8.2
  • 作者:
    Moritani, M.;Nomura, K.;Itakura, M.
  • 通讯作者:
    Itakura, M.
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MORITANI Maki其他文献

MORITANI Maki的其他文献

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{{ truncateString('MORITANI Maki', 18)}}的其他基金

Identification of genetic factor for type 1 diabetes mellitus
1型糖尿病遗传因素的鉴定
  • 批准号:
    22590997
  • 财政年份:
    2010
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Fine mapping of candidate regions identtfied by QTL analysis and functiohal analysis of candidate genes located within the QTL region
通过QTL分析和位于QTL区域内的候选基因的功能分析确定的候选区域的精细定位
  • 批准号:
    19591053
  • 财政年份:
    2007
  • 资助金额:
    $ 2.24万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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