Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats

Aim: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic path...

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Published in:Diabetes, obesity & metabolism obesity & metabolism, 2002-09, Vol.4 (5), p.309-318
Main Authors: Okuno, S., Kondo, M., Yamasaki, Y., Miyao, H., Ono, T., Iwanaga, T., Omori, K., Okano, M., Suzuki, M., Momota, H., Hishigaki, H., Hayashi, I., Goto, Y., Shinomiya, H., Harada, Y., Hirashima, T., Kanemoto, N., Asai, T., Wakitani, S., Takagi, T., Nakamura, Y., Tanigami, A., Watanabe, T. K.
Format: Article
Language:English
Subjects:
Animals
Animals, Congenic
body weight
congenic rat
diabetes
Diabetes Mellitus - genetics
Diabetes Mellitus - metabolism
Diabetic Nephropathies - genetics
Dmo1
dyslipidaemia
histopathology
Hyperglycemia - metabolism
Hyperlipidemias - metabolism
Kidney - ultrastructure
Liver - ultrastructure
Male
obesity
Obesity - genetics
Obesity - metabolism
OLETF rat
Phenotype
QTL
Rats
Rats, Inbred F344
Rats, Inbred OLETF
triglyceride
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Summary:Aim: Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes in the Otsuka Long Evans Tokushima Fatty (OLETF) rat strain. To evaluate possible metabolic and pathological improvements generated by correction of the Dmo1 genetic pathway, we produced congenic lines, in which both OLETF Dmo1 alleles are replaced by the F344‐derived genome. Methods: Congenic animals were produced by introgressing F344‐derived Dmo1 alleles into the OLETF rat. Congenic animals of the fourth generation (BC4) were intercrossed to obtain F1 animals (BC4:F1). Animals of the next generation, BC4:F2, were used for this study. We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344‐derived genome. Seven animals with OLETF‐derived Dmo1 alleles were used as controls. Results: Dmo1‐F344/F344 congenic rats showed significant decreases in body weight, abdominal fat weight, serum triacylglycerols, total cholesterol, food consumption and blood glucose after glucose loading (13%, 39%, 45%, 27%, 18% and 27% respectively; p 
ISSN:1462-8902
1463-1326
DOI:10.1046/j.1463-1326.2002.00217.x