Transgenic rabbits overexpressing growth hormone develop acromegaly and diabetes mellitus

Transgenic rabbits overexpressing growth hormone develop acromegaly and diabetes mellitus
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DOI:
10.1096/fasebj.12.14.1455
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发表时间:
1998-11-01
期刊:
影响因子:
4.8
通讯作者:
Bosch, F
Bosch, F
中科院分区:
生物学2区
文献类型:
--
作者:
Costa, C;Solanes, G;Bosch, F

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用牛生长激素(bGH)基因在肝脏和肾脏中表达的转基因兔研究了慢性GH暴露对非啮齿类动物的长期效应。尽管长期暴露于bGH,转基因兔的体重与对照组相似。然而,在这些动物中观察到头部和四肢增大以及内脏脂肪减少。他们还表现出明显的高胰岛素血症、高血糖症和高胆固醇血症,表明他们出现了胰岛素抵抗。此外,在肝脏、肾脏和骨骼肌中观察到严重的组织病理学改变,包括明显的纤维化。这些解剖学、代谢和组织学改变与肢端肥大症患者中发现的那些非常相似,因此,过表达GH的转基因兔可能是人类疾病的良好模型。
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.