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Gene Review:

Dmo1 - Diabetes Mellitus OLETF QTL 1

Rattus norvegicus

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Disease relevance of Dmo1

We also mapped two additional significant loci, on Chrs 7 and 14, in the (OLETF x F344)F2 cross alone, and designated these three loci as Diabetes mellitus, OLETF type Dmo 1, Dmo2 and Dmo3 respectively [1].
Our extensive genomic scanning with 218 markers revealed nine significant QTLs, including a strong determinant of obesity on chromosome 1 (Dmo1: LOD = 13.99, for body weight) [2].
The chromosome 1 QTL colocalized with Dmo1 (diabetes mellitus, OLETF type 1), a locus previously shown to associate strongly with both fat levels and body weight [3].
1. We have confirmed the Diabetes Mellitus OLETF type I (Dmo1) effect on hyperphagia, dyslipidaemia and obesity in the Otsuka Long-Evans Tokushima Fatty (OLETF) strain [4].

High impact information on Dmo1

Whole-genome scans have identified Dmo1 as a major quantitative trait locus (QTL) for obesity and dyslipidaemia in the Otsuka Long Evans Tokushima Fatty (OLETF) rat [5].
In the third generation of congenic animals, we observed a substantial therapeutic effect of the Dmo1 locus on lipid metabolism, obesity control and plasma glucose homeostasis [5].
2. Within the critical 570 kb region of the Dmo1 locus, we identified the G-protein-coupled receptor gene GPR10 as the causative gene mutated in the OLETF strain [4].
Centrally administered PrRP suppressed the food intake of congenic rats that have a Brown Norway derived Dmo1 region (i.e. with wild-type GPR10), but did not suppress that of the OLETF strain, indicating that GPR10 is without function and could explain hyperphagia in the OLETF strain [4].
1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats [6].

Chemical compound and disease context of Dmo1

3. The Diabetes Mellitus OLETF type I (Dmo1) locus on rat chromosome 1 showed statistically significant involvement in elevations of plasma levels of triglycerides (P = 4.87 x 10(-6) at D1Rat90) and total cholesterol (P = 1.16 x 10(-5) at D1Rat306) [7].

Biological context of Dmo1

5. These analyses have confirmed the importance of Dmo1 in lipid homeostasis at younger ages as well as during overt diabetes, which appears later [7].
A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats [6].
We used 23 BC4:F2 males harbouring homozygous replacement of the OLETF Dmo1 region with the F344-derived genome [8].

References

Genetic dissection of "OLETF", a rat model for non-insulin-dependent diabetes mellitus. Kanemoto, N., Hishigaki, H., Miyakita, A., Oga, K., Okuno, S., Tsuji, A., Takagi, T., Takahashi, E., Nakamura, Y., Watanabe, T.K. Mamm. Genome (1998) [Pubmed]
Genetic dissection of "OLETF," a rat model for non-insulin-dependent diabetes mellitus: quantitative trait locus analysis of (OLETF x BN) x OLETF. Watanabe, T.K., Okuno, S., Oga, K., Mizoguchi-Miyakita, A., Tsuji, A., Yamasaki, Y., Hishigaki, H., Kanemoto, N., Takagi, T., Takahashi, E., Irie, Y., Nakamura, Y., Tanigami, A. Genomics (1999) [Pubmed]
Genetic determinants of plasma triglyceride levels in (OLETF x BN) x OLETF backcross rats. Okuno, S., Watanabe, T.K., Ono, T., Yamasaki, Y., Goto, Y., Miyao, H., Asai, T., Kanemoto, N., Oga, K., Mizoguchi-Miyakita, A., Takagi, T., Takahashi, E., Nakamura, Y., Tanigami, A. Genomics (1999) [Pubmed]
Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat. Watanabe, T.K., Suzuki, M., Yamasaki, Y., Okuno, S., Hishigaki, H., Ono, T., Oga, K., Mizoguchi-Miyakita, A., Tsuji, A., Kanemoto, N., Wakitani, S., Takagi, T., Nakamura, Y., Tanigami, A. Clin. Exp. Pharmacol. Physiol. (2005) [Pubmed]
Effects of Dmo1 on obesity, dyslipidaemia and hyperglycaemia in the Otsuka Long Evans Tokushima Fatty strain. Okuno, S., Watanabe, T.K., Ono, T., Oga, K., Mizoguchi-Miyakita, A., Yamasaki, Y., Goto, Y., Shinomiya, H., Momota, H., Miyao, H., Hayashi, I., Asai, T., Suzuki, M., Harada, Y., Hishigaki, H., Wakitani, S., Takagi, T., Nakamura, Y., Tanigami, A. Genet. Res. (2001) [Pubmed]
A < 1.7 cM interval is responsible for Dmo1 obesity phenotypes in OLETF rats. Watanabe, T.K., Okuno, S., Yamasaki, Y., Ono, T., Oga, K., Mizoguchi-Miyakita, A., Miyao, H., Suzuki, M., Momota, H., Goto, Y., Shinomiya, H., Hishigaki, H., Hayashi, I., Asai, T., Wakitani, S., Takagi, T., Nakamura, Y., Tanigami, A. Clin. Exp. Pharmacol. Physiol. (2004) [Pubmed]
Quantitative trait loci for lipid metabolism in the study of OLETF x (OLETF x Fischer 344) backcross rats. Yamasaki, Y., Watanabe, T.K., Okuno, S., Ono, T., Oga, K., Mizoguchi-Miyakita, A., Goto, Y., Shinomiya, H., Momota, H., Miyao, H., Hayashi, I., Asai, T., Suzuki, M., Harada, Y., Hishigaki, H., Wakitani, S., Takagi, T., Nakamura, Y., Tanigami, A. Clin. Exp. Pharmacol. Physiol. (2000) [Pubmed]
Substitution of Dmo1 with normal alleles results in decreased manifestation of diabetes in OLETF rats. 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. Diabetes, obesity & metabolism. (2002) [Pubmed]

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