Overexpression of Agrt leads to obesity in transgenic mice.

M Graham, JR Shutter, U Sarmiento, I Sarosi, KL Stark - 1997 - cabidigitallibrary.org
M Graham, JR Shutter, U Sarmiento, I Sarosi, KL Stark
1997cabidigitallibrary.org
The mouse Agrt gene, also known as Art and Agrp, contains sequences homologous to the
agouti gene, which causes obesity and diabetes when ectopically expressed. The Agrt
coding sequence under the control of the human β-actin promoter was used to generate
transgenic mice. Transgene expression was found to be correlated with weight gain. Two
independent transgenic lines were established. the transgenic mice did not have yellow
coats, which indicated that Agrt overexpression did not affect melanogenesis. The weights of …
Abstract
The mouse Agrt gene, also known as Art and Agrp, contains sequences homologous to the agouti gene, which causes obesity and diabetes when ectopically expressed. The Agrt coding sequence under the control of the human β-actin promoter was used to generate transgenic mice. Transgene expression was found to be correlated with weight gain. Two independent transgenic lines were established. the transgenic mice did not have yellow coats, which indicated that Agrt overexpression did not affect melanogenesis. The weights of F1 progeny from the 2 transgenic lines were significantly higher (P≤0.05) than those of controls as early as 6 weeks of age. The serum insulin was significantly elevated at 6 weeks and even further elevated at 10 weeks. Hyperglycaemia did not occur at 6 weeks but was observed by 10 weeks in males. Serum levels of corticosterone were normal. The combined weight of the epididymal and peritoneal fat pads was significantly (P≤0.05) increased in transgenic animals. Fat was deposited in the hepatocytes of transgenic mice. Hypertrophied fat cells were present in white and brown adipose tissue. The pancreatic islets of the transgenic mice showed hypertrophy and hyperplasia.
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