We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.

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