Ma Y, Singer D B, Gozman A, Ford D, Chai L, Steinhoff M M, Hansen K, Maizel A L
Department of Pathology, Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA.
Pediatr Nephrol. 2001 Sep;16(9):701-9. doi: 10.1007/s004670100624.
Townes-Brocks syndrome (TBS) is a human genetic disorder with features including urogenital, limb, anal and cardiac malformations associated with mutations 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 associated 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 kidney and brain, with detectable production in thymus and heart. p140 was found in fetal ureteric bud, fetal and postnatal renal tubular epithelium, and renal blastema. In the 14-week fetal testis, the Hsal 1 protein was specifically expressed in the testosterone producing Leydig cells while in adult gonads 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 expression for Hsal 1, and the phenotypic effects associated with TBS, suggest that Hsal 1 plays an important role in the development and functional maintenance 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 in addition to its specific role in Townes-Brocks syndrome.
汤姆斯-布罗克斯综合征（TBS）是一种人类遗传性疾病，其特征包括泌尿生殖系统、肢体、肛门和心脏畸形，与TBS基因Hsal 1的突变有关。为了开始了解Hsal 1蛋白（p140）在正常发育和疾病发病机制中的作用，我们评估了与TBS相关的特定组织中的信使核糖核酸和蛋白质表达。Hsal 1的DNA序列信息预测，这个同源异型的果蝇同源物（Sal）编码一种与转录因子一致的锌指蛋白。Hsal 1的信使核糖核酸在胎儿肾脏和大脑中高度表达，在胸腺和心脏中也有可检测到的产生。p140在胎儿输尿管芽、胎儿和出生后肾小管上皮以及肾胚基中被发现。在14周的胎儿睾丸中，Hsal 1蛋白在产生睾酮的睾丸间质细胞中特异性表达，而在成年性腺中，Hsal 1也在睾丸间质细胞和支持细胞、睾丸精原细胞以及卵巢颗粒细胞中被发现。对肾母细胞瘤的评估显示，该基因产物在其上皮和胚基成分中持续高表达。Hsal 1的这些时空表达模式以及与TBS相关的表型效应表明，Hsal 1在肾脏和性腺的发育及功能维持中起重要作用。此外，Hsal 1基因产物除了在汤姆斯-布罗克斯综合征中发挥特定作用外，可能还在这些器官中发生的特定肿瘤的发病机制中起作用。
