Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the OtsukaLong Evans Tokushima Fatty strain

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fat ty (OLETF) rat. We have produced congenic rats for the Dmo1 locus, using ma rker-assisted speed congenic protocols, enforced by selective removal of ot her QTL regions (QTL-marker-assisted counterselection), to efficiently tran sfer chromosomal segments from non-diabetic Fischer 344 (F344) rats into th e OLETF background. In the third generation of congenic animals, we observe d a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, o besity control and plasma glucose homeostasis. We conclude that single-alle le correction of an impaired genetic pathway can generate a substantial the rapeutic effect, despite the complex polygenic nature of type II diabetic s yndromes.