Identification of susceptibility gene of diabetes mellitus y QTL analysis in the genetic modified mice.
Identification of susceptibility gene of diabetes mellitus y QTL analysis in the genetic modified mice.
批准号:
09470224
负责人:
ITAKURA Mitsuo
金额:
$8.26万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1997
资助国家:
日本
项目状态:
已结题
起止时间:
1997 至 1999
中文摘要
I型和II型糖尿病是一种常见病,也是一个主要的公共卫生问题。为了确定糖尿病的易感基因,我们进行了全基因组数量性状基因座(QTL)分析,以C57BL6/KSJ背景下的db小鼠或NOD-RGP-IL-10TG背景下的NOD-RGP-IL-10TG为研究对象。DB小鼠是人类II型糖尿病的动物模型,表现为高血糖、高胰岛素血症、胰岛素抵抗和肥胖。Db小鼠和非糖尿病C3H品系的F2杂交显示了与糖尿病相关的多种疾病,包括体重、血糖浓度、血浆胰岛素浓度和葡萄糖耐量。我们已经确定了几个与体重和糖耐量相关的QTL。NOD-RGP-IL-10 TG可增强自身免疫性糖尿病,但与C57BL/6杂交的F1小鼠均未出现糖尿病。NOD-RGP-IL-10TG与C57BL/6小鼠回交2次,糖尿病发生率为15%。与db小鼠相似,我们正在对n2代进行全基因组数量性状基因座(QTL)分析。
英文摘要
Type I and II diabetes is a common disease and a major public health problem. To identify the susceptibility gene to diabetes we performed genome-wide quantitative trait loci (QTL) analysis, using db mice in C57BL6/ksj background or NOD-RGP-IL-10 Tg in NOD background. db mouse is an animal model of type II diabetes in human exhibiting hyperglycemia, hyperinsulinemia, insulin resistance, and obesity. F2 intercross between db mice and non-diabetic C3H strain demonstrated a wide variety of diabetes related, including body weight, plasma glucose concentration, plasma insulin concentration, and glucose tolerance. We have identified several QTLs associated with body weight and glucose tolerance. NOD-RGP-IL-10 Tg enhance autoimmune diabetes, but none of the resulting F1 mice outbred to C57BL/6 mice show diabetes. N2 backcross between NOD-RGP-IL-10 Tg and C57BL/6 mice demonstrated 15% incidence of diabetes. Similar to db mice, we are performing genome-wide quantitative trait loci (QTL) analysis for N2 generation.
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Yamaoka T: "Amidophosphoribosyltransferase limits the rate of cell growth-liked de novo purine biosynthesis in the presence of constant capacity of salvage purine biosynthesis." J.Biol.Chem.272. 17719-17725 (1997)
Yamaoka T:“在挽救性嘌呤生物合成能力恒定的情况下,氨基磷酸核糖基转移酶限制了类似细胞生长的从头嘌呤生物合成速率。”
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Kamatani N: "Localization of a gene for familial juvenile Hyperuricemic nephropathy causing undcrecerection-type gout to I6p12 by genome-wide linkage analysis of a large family"Arthritis & Rheumatism. (in press). (2000)
Kamatani N:“通过对一个大家族进行全基因组连锁分析,将导致未排泄型痛风的家族性青少年高尿酸血症肾病基因定位到 I6p12”关节炎
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Yamaoka T: "Hypoplasia of pancreatic islets in transgenic mice expressing activen receptor mutants." J.Clin.Invest.102(2). 294-301 (1998)
Yamaoka T:“表达活性受体突变体的转基因小鼠胰岛发育不全。”
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Yamaoka T: "Amidophosphoribosyl transferase limits the rate of cell growth-liked de novo purine biosynthesis in the presence of constant capacity of salyage purine biosynthesis." J.Biol.Chem.272. 17719-17725 (1997)
Yamaoka T:“在存在恒定的嘌呤生物合成能力的情况下,氨基磷酸核糖基转移酶限制了类似细胞生长的从头嘌呤生物合成的速率。”
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Kamatani N: "Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p 12 by genome-wide linkage analysis of a large family."Arthritis & Rheumatism. (in press). (2000)
Kamatani N:“通过对一个大家族进行全基因组连锁分析,将导致排泄不足型痛风的家族性青少年高尿酸血症肾病基因定位于 16p 12。” 关节炎
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共 15 条
Functional analysis of theENDOGL1 gene as a candidate disease susceptibility gene for T2D by rentivirus vector
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批准号:19591080
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Identification of type 2 diabetes mellitus susceptibility candidate genes in loci detected by QTL analysis of diabetic db mice,
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Identification of susceptibility gene of diabetes mellitus by QTL analysis in the genetic modified mice
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Immunosuppressive role of TGF-β1 against autoimmune destruction of islet β cells and a basic study on islet β cells of NOD-RGP-TGF-β1 Tg
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财政年份:1999
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Analysis of Immunological Destruction Mechanism of Pancreatic Islet B Cells Using a Transgenic Mouse Model
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Development of Gene Therapy for Type I Diabetes Using Cytokine Gene and Pancreatic Islet B Cell-Specific Lymphocytes
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Molecular Analysis of a Glucose-concentration sensing system which Regulates Insulin Gene Expression
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Development of the Methods for Regulated Expression of Transduced Gene in Transkaryotic Gene Therapy
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负责人:ITAKURA Mitsuo
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依托单位:
Molecular Biological Study on Rate-limiting Enzyme DNA of de novo Purine Synthesis by Gene Transfer and Controllable Expression
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负责人:ITAKURA Mitsuo
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