Transgenic rabbits overexpressing growth hormone develop acromegaly and diabetes mellitus.
Transgenic rabbits expressing the bovine growth hormone (bGH) gene in liver and kidney were obtained to study the long-term effects of chronic exposure to GH in nonrodent animals. These rabbits presented high levels of bGH and insulin-like growth factor I in serum. In spite of chronic exposure to bGH, transgenic rabbits had similar body weight to controls. However, enlargement of the head and limbs and reduction of visceral fat were observed in these animals. They also showed marked hyperinsulinemia, hyperglycemia, and hypertriglyceridemia, indicating that they developed insulin resistance. Furthermore, serious histopathological alterations, including marked fibrosis, were observed in liver, kidney, and skeletal muscle. These anatomical, metabolic, and histological alterations closely resemble those found in patients with acromegaly. Thus, transgenic rabbits overexpressing GH may be a good model of the human disease.
Costa
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C
Departament de Bioquimica i Biologia Molecular, Facultat de Veterinària, Universitat Autònoma de Barcelona, 08193-Bellaterra, Spain.
Solanes
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G
Visa
J
J
Bosch
F
F
D000172:Acromegaly / Q000097:blood / Q000235:genetics* / Q000473:pathology; D000818:Animals; D030801:Animals, Genetically Modified; D001824:Body Constitution; D002417:Cattle; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D013006:Growth Hormone / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000235:genetics
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D019764:Phosphoenolpyruvate Carboxykinase (ATP)