title: Nephrocystin: gene expression and sequence conservation between human, mouse, and Caenorhabditis elegans.
abstract: 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 contains a src-homology 3 domain. To study tissue expression and analyze amino acid 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 widespread but relatively weak NPHP1 expression in the human adult. In the adult mouse there is strong expression in testis. This expression occurs specifically in cell stages of the first meiotic division and thereafter. In situ hybridization to whole mouse embryos demonstrated widespread and uniform expression at all developmental stages. Amino acid sequence conservation studies in human, mouse, and Caenorhabditis elegans show that in nephrocystin the src-homology 3 domain is embedded in a novel context of other putative domains of protein-protein interaction, such as coiled-coil and E-rich domains. It is concluded that for multiple putative protein-protein interaction domains of nephrocystin, sequence conservation dates back at least to Caenorhabditis elegans. The previously described discrepancy between widespread tissue expression and the restriction of symptoms to the kidney has now been confirmed by an in-depth expression study.
authors.affiliation: University Children's Hospital, Freiburg University, Freiburg, Germany.
authors.forename: Edgar
authors.initials: E
authors.lastname: Otto
authors.affiliation: Max-Planck Institute for Immunobiology, Freiburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Kispert
authors.affiliation: University Children's Hospital, Freiburg University, Freiburg, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schätzle
authors.affiliation: Max-Planck Institute for Immunobiology, Freiburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Lescher
authors.affiliation: University Children's Hospital, Freiburg University, Freiburg, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rensing
authors.affiliation: University Children's Hospital, Freiburg University, Freiburg, Germany.
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics*; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D015870:Gene Expression; D006801:Humans; D008565:Membrane Proteins; D051379:Mice / Q000235:genetics*; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics*; D016415:Sequence Alignment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; C108725:NPHP1 protein, human; C534985:Nphp1 protein, mouse; D011506:Proteins