CHROMOSOMAL ASSIGNMENT OF LOCI CONCERNING TYPE II DIABETES IN RAT

大冢Long-Evans德岛脂肪（OLETF）大鼠是人类轻度肥胖非胰岛素依赖型糖尿病（NIDDM）的最佳模型。OLETF大鼠在大约年龄时表现为自发性糖尿病伴多尿和多饮。20周。在SPF屏障群体中进行oletfxf344交叉杂交。30周龄时进行口服葡萄糖耐量试验（OGTT）。为了分析F2后代，大约。300个微卫星标记从res . gene . inc .购买。，然后用PCR技术扩增DNA片段。PCR产物在3-4%MetaPhor ^<iTM>琼脂糖凝胶上电泳。采用MAPMAKER/QTL程序进行连锁分析。在OLETF大鼠与正常血糖控制菌株F344的杂交连锁研究中，发现了5个基因Niddm4、Niddm5、Niddm6、Niddm7和NiddmX的定位，这些基因对F2群体OGTT的血糖变化有重要影响。Niddm4、Niddm5、Niddm6和Niddm7被分配到大鼠常染色体，而NiddmX被分配到x染色体。其中，染色体上的NiddmX是OLETF大鼠NIDDDM发病的主要位点。我们还在常染色体上发现了一个影响体重的主要基因座Weight2。LOD评分为3.0或更高的连锁位点命名。我们的发现表明OLETF大鼠的NIDDM是由相当多的基因座引起的，并提示肥胖的NIDDM可能也部分受人类X染色体上的基因影响。另一个伴随体重过度增长的因素可能是OLETF大鼠NIDDM发病的原因。

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.