RGD Reference Report - Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat. - Rat Genome Database

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Mutated G-protein-coupled receptor GPR10 is responsible for the hyperphagia/dyslipidaemia/obesity locus of Dmo1 in the OLETF rat.

Authors: Watanabe, TK  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 
Citation: Watanabe TK, etal., Clin Exp Pharmacol Physiol. 2005 May-Jun;32(5-6):355-66.
RGD ID: 1641829
Pubmed: (View Article at PubMed) PMID:15854142
DOI: Full-text: DOI:10.1111/j.1440-1681.2005.04196.x

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. The critical interval was narrowed down to 570 kb between D1Got258 to p162CA1 by segregation analyses using congenic lines. 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. The ATG translation initiation codon of GPR10 is changed into ATA in this strain and, so, is unavailable for the initiation of translation. 3. The GPR10 protein has a cognate ligand, namely prolactin-releasing peptide (PrRP). 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. Moreover, when restricted in food volume to the same level consumed by the congenic strain, OLETF rats showed few differences in the parameters of dyslipidaemia and obesity compared with congenic strains. 5. Taken together, these results demonstrate that the mutated GPR10 receptor is responsible for the hyperphagia leading to obesity and dyslipidaemia in the obese diabetic strain rat.

Annotation

Disease Annotations    
obesity  (IAGP,IDA,ISO)

Gene Ontology Annotations    

Biological Process

Molecular Function

Molecular Pathway Annotations    
obesity pathway  (IMP,ISO)

Phenotype Annotations    

Mammalian Phenotype
obese  (IAGP)
polyphagia  (IAGP)
Objects Annotated

Genes (Rattus norvegicus)
Prlh  (prolactin releasing hormone)
Prlhr  (prolactin releasing hormone receptor)

Genes (Mus musculus)
Prlh  (prolactin releasing hormone)
Prlhr  (prolactin releasing hormone receptor)

Genes (Homo sapiens)
PRLH  (prolactin releasing hormone)
PRLHR  (prolactin releasing hormone receptor)

Objects referenced in this article
Strain OLETF Otsuka Long-Evans Tokushima fatty Rattus norvegicus

Additional Information