SPATIALLY RESTRICTED EXPRESSION OF SET MESSENGER-RNA IN DEVELOPING RAT-KIDNEY

A somatic translocation event fusing the novel gene set to the putativ e oncogene can has been implicated in the development of acute nonlymp hocytic leukemia in humans. In this study, full-length cDNAs highly ho mologous with human set were cloned from a rat neonatal kidney library . The expression pattern of set mRNA was then examined in developing r at kidney. Two groups of set cDNAs (alpha and beta) with different tra nslation initiation sites and open reading frames of 867 and 831 bp, r espectively, were found. The predicted protein products are 33,385 and 32,085 Da in size and contain similar to 30% acidic residues, over ha lf of them clustered at the COOH terminal, thus forming a long acidic tail. No signal peptide or membrane-spanning domains were identified, suggesting an intracellular protein product. By ribonuclease protectio n assay, both alpha and beta variants of set were expressed in kidney. On Northern blots of total kidney RNA, 3.0- and 2.2-kb mRNAs hybridiz ed with the labeled set cDNA probe. Expression of both transcripts was four- to eightfold greater in neonatal compared with adult rat kidney . When neonatal rat kidneys were examined for set mRNA expression by i n situ hybridization with S-35-labeled riboprobe, expression was dense ly localized in the cortical region of morphogenesis over primitive ne phron structures, including S-shaped bodies. Thus mRNA for Set, a puta tive intracellular protein involved in leukemogenesis, is expressed in kidney. Because expression of set mRNA appears to be highly regulated both spatially and temporally in the developing kidney and because it is localized to developing nephron structures, it is postulated that the Set protein may be a participant in the process of early nephron m orphogenesis.