CHROMOSOMAL ASSIGNMENT OF LOCI CONCERNING TYPE II DIABETES IN RAT

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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.