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小鼠肾素基因在皮下结缔组织中的表达。

Expression of murine renin genes in subcutaneous connective tissue.

作者信息

Sigmund C D, Jones C A, Mullins J J, Kim U, Gross K W

机构信息

Department of Molecular, Roswell Park Cancer Institute, Buffalo, NY 14263.

出版信息

Proc Natl Acad Sci U S A. 1990 Oct;87(20):7993-7. doi: 10.1073/pnas.87.20.7993.

Abstract

A renin promoter-large tumor antigen (T antigen) fusion gene was constructed to provide a reporter function for renin expression in transgenic mice. These transgenic mice gave rise to tumors in subcutaneous soft tissue, which was attributed to transgene expression at this site. An immunohistochemical analysis of transgenic fetuses from several independent lines revealed scattered T-antigen-containing mesenchymal cells and fibroblasts in the subcutaneous layer of the skin between the panniculus carnosus muscle of the skin and the skeletal muscle of the body wall. This localization is consistent with the location of overt tumorigenesis in adult mice. This pattern was specific for the renin-T antigen fusion gene as no immunohistochemical staining was observed in transgenic fetuses containing a heterologous promoter-T antigen fusion gene. Northern blot analysis of tumor RNA indicated that most of the tumors expressed both T antigen and the endogenous renin gene Ren-1c. In addition, when multiple renin genes were introduced by crossing transgenic mice with nontransgenic DBA/2J mice, which contain another allele of the Ren-1 locus as well as the duplicated locus Ren-2, the resultant tumors expressed the Ren-2 gene. Northern blots were then used to analyze renin expression in the subcutaneous tissue of normal mice. Fully processed renin mRNA was detected in eviscerated 15.5-day postcoitus fetal and newborn carcasses and in newborn skin. Our data indicate that there is a renin-expressing cell population in fetal and newborn subcutaneous tissue.

摘要

构建了一种肾素启动子 - 大肿瘤抗原(T抗原)融合基因,用于在转基因小鼠中为肾素表达提供报告功能。这些转基因小鼠在皮下软组织中产生肿瘤,这归因于该位点的转基因表达。对来自几个独立品系的转基因胎儿进行免疫组织化学分析,发现在皮肤的肉膜肌与体壁骨骼肌之间的皮肤皮下层中有散在的含T抗原的间充质细胞和成纤维细胞。这种定位与成年小鼠明显肿瘤发生的位置一致。这种模式对于肾素 - T抗原融合基因是特异的,因为在含有异源启动子 - T抗原融合基因的转基因胎儿中未观察到免疫组织化学染色。对肿瘤RNA的Northern印迹分析表明,大多数肿瘤同时表达T抗原和内源性肾素基因Ren-1c。此外,当通过将转基因小鼠与非转基因DBA/2J小鼠杂交引入多个肾素基因时,非转基因DBA/2J小鼠含有Ren-1位点的另一个等位基因以及重复的Ren-2位点,所产生的肿瘤表达Ren-2基因。然后使用Northern印迹分析正常小鼠皮下组织中的肾素表达。在15.5天交配后胎儿和新生动物的去内脏尸体以及新生皮肤中检测到完全加工的肾素mRNA。我们的数据表明,在胎儿和新生动物的皮下组织中存在表达肾素的细胞群体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9c2/54878/e0919bfdaec5/pnas01045-0205-a.jpg

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