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CHROMOSOMAL ASSIGNMENT OF LOCI CONCERNING TYPE II DIABETES IN RAT

大鼠 II 型糖尿病基因座的染色体分配

基本信息

批准号：
05454688
负责人：
MATSUMOTO Kozo
金额：
$ 4.29万
依托单位：
UNIVERSITY OF TOKUSHIMA
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454688/
关键词：
DIABETES NIDDM RAT MAPPING CHROMOSOME rat microsatellite diabetes chromosomal mapping

项目摘要

The Otsuka Long-Evans Tokushima Fatty(OLETF)rat is the best model for human non-insulin dependent diabetes mellitus(NIDDM)with mild obese body. OLETF rats display spontaneous diabetes with polyuria, and polydipsia at the age of approx.20 weeks. The cross between OLETFxF344intercrosses was conducted in a SPF barrier colony. The oral glucose tolerance test(OGTT)was performed at the age of 30 weeks old. To analyze F2 progeny, approx.300 microsatellite markers were purchased from Res.Genet.Inc., and then DNA fragments were amplified by the PCR techniques.PCR products were electrophoresed on 3-4%MetaPhor ^<iTM> Agarose gel. Linkage analysis was performed using the MAPMAKER/QTL computer program. Linkage studies in crosses between the OLETF rat and the normal blood glucose control strain F344 have led to the localization of five genes, Niddm4, Niddm5, Niddm6, Niddm7, and NiddmX,that contribute significantly to blood glucose variation by OGTT in F2 population. Niddm4, Niddm5, Niddm6, and Niddm7, were assigned to rat autosomal chromosomes, while NiddmX was assigned to X-chromosome. Especially, NiddmX on chromosomeX was the majorlocus for the onset of NIDDDM in OLETF rats. Also we identify one majorlocus Weight2 affecting body weight on an autosomal chromosome. The loci names were given to linkages with LOD scores of 3.0 or more.Our finding indicates that NIDDM in OLETF rats is caused by considerable multiple loci, and would be suggestive that obese NIDDM might be partly affected by a gene on chromosome X in human, as well. The other factor accompanied by excess growth of body weight may be responsible for the onset of NIDDM in OLETF rat.

大冢长埃文斯德岛肥胖（OLETF）大鼠是研究人非胰岛素依赖型糖尿病（NIDDM）的最佳动物模型。OLETF大鼠在约20周龄时表现出自发性糖尿病伴多尿和多饮。在SPF屏障菌落中进行OLETFxF 344互交之间的杂交。在30周龄时进行口服葡萄糖耐量试验（OGTT）。为了分析F2后代，从Res. Genet. Inc.购买约300个微卫星标记，PCR产物经3-4%MetaPhor<iTM>琼脂糖凝胶电泳后，进行琼脂糖凝胶电泳。利用MAPMAKER/QTL计算机程序进行连锁分析。对OLETF大鼠和正常血糖控制菌株F344之间的杂交进行的连锁研究已经定位了五个基因：Niddm 4、Niddm 5、Niddm 6、Niddm 7和NiddmX，这些基因对F2群体中OGTT的血糖变异有显着贡献。Niddm 4、Niddm 5、Niddm 6和Niddm 7被分配到大鼠常染色体，而NiddmX被分配到X染色体。特别是X染色体上的NiddmX是OLETF大鼠NIDDDM发病的主要位点。我们还确定了一个主基因座Weight 2影响体重的常染色体上。我们的发现表明OLETF大鼠的NIDDM是由相当多的多个位点引起的，并且提示肥胖NIDDM可能部分地受到人类X染色体上的基因的影响。另一个因素伴随着体重的过度增长可能是导致OLETF大鼠发生NIDDM的原因。