UNILATERAL NEPHRECTOMY INDUCES THE EXPRESSION OF THE WILMS-TUMOR GENEIN THE CONTRALATERAL KIDNEY OF THE ADULT-RAT

Purpose: The tumor suppressor gene WT-1 encodes a nuclear deoxyribonuc leic acid binding protein that is a transcriptional regulator. This ge ne is commonly deleted or defective in Wilms tumors and the Denys-Dras h syndrome, Recently WT-1 was demonstrated to be essential for the dev elopment of the urogenital tract. We determined whether we could induc e WT-1 expression in mature kidneys induced to grow by performing cont ralateral nephrectomy in mature rats. Materials and Methods: Northern analysis with a (32)phosphorus-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. Results: Transcript levels of WT-1 in the rat kidney decreased from day 0 (day of birth) to day 16, after w hich WT-1 transcripts were undetectable in the normal rat kidney. Unil ateral nephrectomy in the adult male Sprague-Dawley rat (250 to 300 gm .) induced the expression of WT-1 ribonucleic acid in the contralatera l kidney to detectable levels by Northern analysis 0.25 hours after ne phrectomy, Subsequently levels of WT-1 ribonucleic acid decreased prog ressively 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. Conclusions: These data suggest that; the WT-1 g ene product is involved in normal renal growth in the adult and develo ping rat kidney.