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Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia

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 spontan...

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Published in:American journal of physiology: endocrinology and metabolism 2013-08, Vol.305 (3), p.E451-E463
Main Authors: Nakahara, Keiko, Bannai, Makoto, Maruyama, Keisuke, Suzuki, Yoshihiro, Okame, Rieko, Murakami, Noboru
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container_title American journal of physiology: endocrinology and metabolism
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description 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.
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subjects Adipose Tissue - diagnostic imaging
Adipose Tissue - pathology
Age
Animals
Body fat
Body Weight - physiology
Cholesterol - blood
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - physiopathology
Diabetes Mellitus, Type 2 - psychology
Disease Models, Animal
Eating - drug effects
Eating - genetics
Eating - physiology
Genotype & phenotype
Ghrelin - blood
Glucose Tolerance Test
Hemodynamics - physiology
Hyperphagia - genetics
Hyperphagia - psychology
Leptin - blood
Leptin - pharmacology
Metabolic syndrome
Metabolic Syndrome - genetics
Metabolic Syndrome - physiopathology
Metabolic Syndrome - psychology
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mutation
Mutation - physiology
Obesity
Obesity - blood
Obesity - genetics
Obesity - psychology
Real-Time Polymerase Chain Reaction
Receptors, Leptin - biosynthesis
Receptors, Leptin - genetics
Rodents
Tomography, X-Ray Computed
Triglycerides - blood
title Characterization of a novel genetically obese mouse model demonstrating early onset hyperphagia and hyperleptinemia
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