Sharma P M, Yang X, Bowman M, Roberts V, Sukumar S
Molecular Biology of Breast Cancer Laboratory, Salk Institute of Biological Studies, La Jolla, California 92037.
Cancer Res. 1992 Nov 15;52(22):6407-12.
In an effort to study the molecular basis of kidney development and carcinogenesis, we isolated complementary DNA clones of the rat homologue of the human Wilms' tumor gene, WT-1. When compared to the predicted sequence of the human WT-1 polypeptide, the rat WT-1 amino acid sequence is highly conserved (> 97%), except for the loss of one amino acid. In situ mRNA hybridization experiments localized WT-1 expression to the glomerular cells in the kidney during embryogenesis and the Sertoli cells of the testis. Similar to expression in humans and mice, WT-1 mRNA expression in the rat kidney and testis is developmentally regulated. In addition, two novel sites of specific high level WT-1 mRNA expression were seen. One is an area in the spinal cord where high level expression occurs throughout embryonic development. The second is the area postrema in the brain where localized expression continues through adulthood, suggesting a functional role for WT-1 in rat brain.
为了研究肾脏发育和致癌作用的分子基础，我们分离了人类威尔姆斯瘤基因WT-1大鼠同源物的互补DNA克隆。与人类WT-1多肽的预测序列相比，大鼠WT-1氨基酸序列高度保守（>97%），只是缺失了一个氨基酸。原位mRNA杂交实验将WT-1的表达定位到胚胎发育期间肾脏中的肾小球细胞以及睾丸的支持细胞。与人类和小鼠中的表达相似，大鼠肾脏和睾丸中WT-1 mRNA的表达受发育调控。此外，还发现了两个特定的高水平WT-1 mRNA表达的新位点。一个是脊髓中在整个胚胎发育过程中都有高水平表达的区域。另一个是脑中的最后区，其局部表达持续到成年期，这表明WT-1在大鼠脑中具有功能作用。
