@article{2fcf56a49fe44f38a88343faa0e4f41e,
title = "Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination",
abstract = "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 β-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and β-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 β-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.",
author = "Otto, {Edgar A.} and Bernhard Schermer and Tomoko Obara and O'Toole, {John F.} and Hiller, {Karl S.} and Mueller, {Adelheid M.} and Ruf, {Rainer G.} and Julia Hoefele and Frank Beekmann and Daniel Landau and Foreman, {John W.} and Goodship, {Judith A.} and Tom Strachan and Andreas Kispert and Wolf, {Matthias T.} and Gagnadoux, {Marie F.} and Hubert Nivet and Corinne Antignac and Gerd Walz and Drummond, {Iain A.} and Thomas Benzing and Friedhelm Hildebrandt",
note = "Funding Information: We thank the affected individuals and their families for participation, J. Robillard for discussion, R.H. Lyons and A. Imm for large-scale sequencing and P. Cochat for contribution of clinical data on individuals A8 and A10. F.H., G.W. and T.B. are supported by Sonderforschungsbereich 592 of the German Research Foundation and by DFG grants to T.B. and G.W.; I.A.D. and T.O. are supported by grants from the US National Institutes of Health to I.A.D.",
year = "2003",
month = aug,
day = "1",
doi = "10.1038/ng1217",
language = "אנגלית",
volume = "34",
pages = "413--420",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Research",
number = "4",
}