Hsal I is related to kidney and gonad development and is expressed in Wilms tumor

Townes-Brocks syndrome (TBS) is a human genetic disorder with features incl uding urogenital, limb, anal and cardiac malformations associated with muta tions of the TBS gene, Hsal 1. To begin to understand the role of the Hsal 1 protein (p140) in both normal development and disease pathogenesis, both message and protein expression were evaluated in specific tissues associate d with TBS. DNA sequence information for Hsal 1 predicts that this homeotic , Drosophila homologue (Sal) encodes a zinc-finger protein consistent with a transcription factor. mRNA for Hsal 1 was highly expressed in fetal kidne y and brain, with detectable production in thymus and heart. p140 was found in fetal ureteric bud, fetal and postnatal renal tubular epithelium, and r enal blastema. In the 14-week fetal testis, the Hsal 1 protein was specific ally expressed in the testosterone producing Leydig cells while in adult go nads Hsal 1 was also found in both Leydig and Sertoli cells, spermatogonia of the testis, and granulosa cells of the ovary. Evaluation of Wilms tumor revealed consistently high expression of the gene product in the epithelial and blastemal components. These spatial and temporal patterns of expressio n for Hsal 1, and the phenotypic effects associated with TBS, suggest that Hsal 1 plays an important role in the development and functional maintenanc e of the kidney and gonads. Furthermore, the Hsal 1 gene product may play a part in the pathogenesis of specific neoplasms occurring in these organs i n addition to its specific role in Townes-Brocks syndrome.