Unilateral nephrectomy induces the expression of the Wilms tumor gene in the contralateral kidney of the adult rat

The tumor suppressor gene WT-1 encodes a nuclear deoxyribonucleic acid binding protein that is a transcriptional regulator. This gene is commonly deleted or defective in Wilms tumors and the Denys-Drash syndrome. Recently WT-1 was demonstrated to be essential for the development of the urogenital tract. We determined whether we could induce WT-1 expression in mature kidneys induced to grow by performing contralateral nephrectomy in mature rats.Northern analysis with a 32phosphorus-labeled antisense riboprobe synthesized by in vitro transcription of a 731 bp complementary deoxyribonucleic acid insert spanning exons 1 to 7 of the rat WT-1 in a pT7 Blue vector was used to demonstrate the expression of WT-1 in the developing and adult Sprague-Dawley rat kidney.Transcript levels of WT-1 in the rat kidney decreased from day 0 (day of birth) to day 16, after which WT-1 transcripts were undetectable in the normal rat kidney. Unilateral nephrectomy in the adult male Sprague-Dawley rat (250 to 300 gm.) induced the expression of WT-1 ribonucleic acid in the contralateral kidney to detectable levels by Northern analysis 0.25 hours after nephrectomy. Subsequently levels of WT-1 ribonucleic acid decreased progressively to undetectable by 3 hours after nephrectomy. Expression of this gene was not detected in the normal kidneys of adult rats or sham operated adult rats.These data suggest that the WT-1 gene product is involved in normal renal growth in the adult and developing rat kidney.