Nephrocystin: Gene expression and sequence conservation between human, mouse, and Caenorhabditis elegans

Juvenile nephronophthisis, an autosomal recessive cystic kidney disease, is the primary genetic cause for chronic renal failure in children. The gene (NPHP1) for nephronophthisis type 1 has recently been identified. Its gene product, nephrocystin, is a novel protein of unknown function, which contai ns a src-homology 3 domain. To study tissue expression and analyze amino ac id sequence conservation of nephrocystin, the full-length murine Nphp1 cDNA sequence was obtained and Northern and in situ hybridization analyses were performed for extensive expression studies. The results demonstrate widesp read but relatively weak NPHP1 expression in the human adult. In the adult mouse there is strong expression in testis. This expression occurs specific ally in cell stages of the first meiotic division and thereafter. bl situ h ybridization to whole mouse embryos demonstrated widespread and uniform exp ression at all developmental stages. Amino acid sequence conservation studi es in human, mouse, and Caenorhabditis elegans show that in nephrocystin th e src-homology 3 domain is embedded in a novel context of other putative do mains of protein-protein interaction, such as coiled-coil and E-rich domain s. It is concluded that for multiple putative protein-protein interaction d omains of nephrocystin, sequence conservation dates back at least to Caenor habditis elegans. The previously described discrepancy between widespread t issue expression and the restriction of symptoms to the kidney has now been confirmed by an in-depth expression study.