Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

Journal Article (Journal Article)

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.

Full Text

Duke Authors

Cited Authors

  • Otto, EA; Schermer, B; Obara, T; O'Toole, JF; Hiller, KS; Mueller, AM; Ruf, RG; Hoefele, J; Beekmann, F; Landau, D; Foreman, JW; Goodship, JA; Strachan, T; Kispert, A; Wolf, MT; Gagnadoux, MF; Nivet, H; Antignac, C; Walz, G; Drummond, IA; Benzing, T; Hildebrandt, F

Published Date

  • August 2003

Published In

Volume / Issue

  • 34 / 4

Start / End Page

  • 413 - 420

PubMed ID

  • 12872123

Pubmed Central ID

  • PMC3732175

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng1217


  • eng

Conference Location

  • United States