Glomerulosclerosis and renal cysts in mice transgenic for the early region of SV40.
Glomerulosclerosis and renal cysts in mice transgenic for the early region of SV40.
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DOI：
10.1038/ki.1987.283
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发表时间：
1987-12
影响因子：
19.6
通讯作者：
Karen Mackay;L. Striker;Carl A. Pinkert;Ralph L. Brinster;G. E. Striker
中科院分区：
文献类型：
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作者：
Karen Mackay;L. Striker;Carl A. Pinkert;Ralph L. Brinster;G. E. Striker
SV40 早期区域转基因小鼠的肾小球硬化和肾囊肿。大量证据表明，遗传决定因素在多种人类和实验诱发的肾脏疾病的发病机制中发挥着重要作用。然而，没有确切的数据表明哪些基因或基因类型可以诱发或促进肾脏疾病。最近获得的对动物遗传背景进行特定改变的能力提供了独特的机会来评估给定基因对感兴趣器官的结构和功能的影响。这种修饰已在转基因小鼠的创建中进行。我们检查了编码大 T 抗原的转基因小鼠，该基因存在于猿猴病毒 40 (SV40) 的早期区域。大多数动物都存在肾脏病变。虽然观察到的肾脏病变的类型和严重程度存在一些异质性，但大多数老年小鼠表现出肾小球硬化和/或增殖性肾小管病变，其中一些与多个大肾小管囊肿相关。这些病变在转基因小鼠中的出现表明，控制细胞增殖的基因的肾脏表达可能与肾小球硬化和肾囊肿的发展有关。这些发现表明其他转化基因或癌基因在人类和其他动物模型的肾小球硬化和囊性肾病的发病机制中可能发挥作用。
Glomerulosclerosis and renal cysts in mice transgenic for the early region of SV40. Considerable evidence indicates that genetic determinants play a major role in the pathogenesis of a variety of human and experimentally-induced renal diseases. There are, however, no firm data to indicate which genes or types of genes can induce or promote renal disease. The recently acquired ability to make specific alterations in the genetic background of an animal affords a unique opportunity to assess the effect(s) of a given gene on the structure and function of an organ of interest. Such modifications have been carried out in the creation of transgenic mice. We examined mice transgenic for the transforming gene encoding large T-antigen which is present in the early region of simian virus 40 (SV40). Renal lesions were present in most animals. While there was some heterogeneity in the type and severity of the renal lesions observed, a majority of the older mice displayed glomerulosclerosis and/or proliferative tubular lesions which in some were associated with multiple, large tubular cysts. The appearance of these lesions in mice transgenic for a transforming gene suggests that renal expression of a gene which controls cell proliferation may be associated with the development of glomerulosclerosis and renal cysts. These findings indicate a possible role for other transforming genes, or oncogenes, in the pathogenesis of glomerulosclerosis and cystic renal disease in humans and other animal models.