title: Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia.
abstract: Obesity is a critical risk factor for the development of metabolic syndrome, and many obese animal models are used to investigate the mechanisms responsible for the appearance of symptoms. To establish a new obese mouse model, we screened ∼13,000 ICR mice and discovered a mouse demonstrating spontaneous obesity. We named this mouse "Daruma" after a traditional Japanese ornament. Following the fixation of the genotype, these animals exhibited obese phenotypes according to Mendel's law of inheritance. In the Daruma mouse, the leptin receptor gene sequence carried two base mutations that are good candidates for the variation(s) responsible for the obese phenotype. The Daruma mice developed characteristic visceral fat accumulation at 4 wk of age, and the white adipose and liver tissues exhibited increases in cell size and lipid droplets, respectively. No histological abnormalities were observed in other tissues of the Daruma mice, even after the mice reached 25 wk of age. Moreover, the onset of impaired leptin signaling was early and manifested as hyperleptinemia and hyperinsulinemia. Pair feeding completely inhibited obesity, although these mice rapidly developed hyperphagia and obesity followed by hyperleptinemia when pair feeding ceased and free-access feeding was permitted. Therefore, the Daruma mice exhibited unique characteristics and may be a good model for studying human metabolic syndrome.
authors.affiliation: Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakahara
authors.forename: Makoto
authors.initials: M
authors.lastname: Bannai
authors.forename: Keisuke
authors.initials: K
authors.lastname: Maruyama
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Rieko
authors.initials: R
authors.lastname: Okame
authors.forename: Noboru
authors.initials: N
authors.lastname: Murakami
mesh_terms: D000273:Adipose Tissue / Q000000981:diagnostic imaging / Q000473:pathology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D054439:Ghrelin / Q000097:blood; D005951:Glucose Tolerance Test; D006439:Hemodynamics / Q000502:physiology; D006963:Hyperphagia / Q000235:genetics* / Q000523:psychology; D020738:Leptin / Q000097:blood* / Q000494:pharmacology; D024821:Metabolic Syndrome / Q000235:genetics / Q000503:physiopathology / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D009154:Mutation / Q000502:physiology; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000523:psychology; D060888:Real-Time Polymerase Chain Reaction; D054411:Receptors, Leptin / Q000096:biosynthesis / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D054439:Ghrelin; D020738:Leptin; D054411:Receptors, Leptin; D014280:Triglycerides; D002784:Cholesterol
keywords: leptin resistance; model animal; mutation