A novel line of transgenic mice (RSV/LTR-bGH) expressing growth hormone in cardiac and striated muscle.

Growth regulation Pub Date : 1995-06-01
F G Conti, R Powell, L Pozzi, G Zezze, T Faraggiana, F Gannon, A Fabbrini
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Abstract

In order to further investigate the deleterious effects of GH overexpression, we generated a novel line of transgenic mice featuring stable and specific expression of bovine GH in the heart and striated muscle. A DNA construct, containing a region with promoter activity from the Long Terminal Repeat of Rous Sarcoma Virus (RSV-LTR) and the entire structural gene of bovine GH (bGH), was microinjected by standard techniques in male pronuclei of fertilized mice eggs. Transgenic mice expressed bGH mRNA in the heart and striated muscle starting at 5-6 weeks of age. They featured circulating levels of a 22 kDa form of bGH up to 700 ng/ml and enhanced growth starting at 6 weeks of age. No pathologic changes of the myocardium and striated muscle fibers, other than hypertrophy, were noticed, although severe glomerulosclerosis and liver alteration occurred in older mice. Future studies on this new line of transgenic GH mice and integration with the existing data might improve our understanding of the molecular mechanism underlying the detrimental effects of elevated GH levels on various organs and functions.

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在心肌和横纹肌中表达生长激素的转基因小鼠(RSV/LTR-bGH)的新品系。
为了进一步研究生长激素过表达的有害影响,我们培育了一种新的转基因小鼠系,在心脏和横纹肌中稳定和特异性地表达牛生长激素。采用标准技术将含有劳斯肉瘤病毒(RSV-LTR)长末端重复序列启动子活性区域和牛生长激素(bGH)整个结构基因的DNA构建体微注射到小鼠受精卵的雄性原核中。转基因小鼠从5-6周龄开始在心脏和横纹肌中表达bGH mRNA。他们的特点是22 kDa形式的bGH循环水平高达700 ng/ml,并在6周龄开始促进生长。除肥大外,未见心肌和横纹肌纤维的病理改变,尽管在老年小鼠中发生了严重的肾小球硬化和肝脏改变。未来对这一新的转基因生长激素小鼠的研究以及与现有数据的整合可能会提高我们对生长激素水平升高对各种器官和功能有害影响的分子机制的理解。
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