权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Genetic analysis of diabetes in SMXA recombinant inbred strain of mice.

SMXA重组近交系小鼠糖尿病的遗传分析。

基本信息

批准号：
11556024
负责人：
HORIO Fumihiko
金额：
$ 4.86万
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：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Type 2 diabetes in humans is not a single gene disorder, but rather it is brought about by the interaction of multiple genes and environmental factors. Recombinant inbred (RI) strains are a powerful tool for analyzing not only single genetic traits, but also multifactorial genetic traits. By using the SMXA RI mice, we genetically dissected diabetes-related traits (BMI, non-fasting blood glucose concentration, and blood glucose concentration during IPGTT). In this study, all mice were fed the high-carbohydrate diet, because feeding this diet minimizes the variation of glucose tolerance in each strain. The parental strains, SM/J and A/J, were non-diabetic, and the differences of the mean values on diabetes-related traits were small. On the other hand, "notable differences" in the mean values of some diabetes-related traits were observed in 19 SMXA RI strains. Several SMXA RI strains showed distinct impaired glucose tolerance and hyperglycemia. QTL analysis revealed six diabetes-related loci on four chromosomes which exceeding the threshold for suggestive level. Especially, a locus on Chr 10 concerning non-fasting blood glucose concentration, was over significant threshold. The A/J-derived genome at two loci on Chr 2 and 18, oppositely the SM/J-derived genome at one locus on Chr 10, contributed to the impairment of glucose tolerance and/or the increase of blood glucose concentration. The present study indicate that the I combinations between silent SM/J and A/J allele can appear to elicit hyperglycemia and impaired glucose tolerance. Genetic dissection of this kind of diabetogenesis may contribute to understand the complex mode of inheritance in human type 2 diabetes.

人类2型糖尿病并不是一种单基因疾病，而是多种基因与环境因素共同作用的结果。重组自交系（RI）是分析单因子遗传性状和多因子遗传性状的有力工具。通过使用SMXA RI小鼠，我们对糖尿病相关性状（BMI、非空腹血糖浓度和IPGTT期间的血糖浓度）进行了遗传解剖。在这项研究中，所有小鼠都被喂食高碳水化合物饮食，因为喂食这种饮食可以最大限度地减少每个品系的葡萄糖耐量变化。亲本SM/J和A/J均为非糖尿病品系，其糖尿病相关性状均值差异较小。另一方面，在19个SMXA RI品系中，一些糖尿病相关性状的平均值存在“显著差异”。一些SMXA RI菌株表现出明显的糖耐量受损和高血糖。QTL分析显示，4条染色体上6个与糖尿病相关的位点超过提示阈值。特别是，Chr 10上一个与非空腹血糖浓度有关的位点超过了显著阈值。A/ j衍生基因组位于Chr 2和18上的两个位点，而SM/ j衍生基因组位于Chr 10上的一个位点，导致糖耐量受损和/或血糖浓度升高。目前的研究表明沉默的SM/J和A/J等位基因之间的I组合可能引起高血糖和糖耐量受损。对这类糖尿病发生的基因解剖有助于理解人类2型糖尿病复杂的遗传模式。