Mutations in Inversin cause Nephronophthisis Type 2, linking Cystic Kidney Disease to the Function of Primary Cilia and Left-Right Axis Determination
dc.contributor.author | Otto, EA | |
dc.contributor.author | Schermer, B | |
dc.contributor.author | Obara, T | |
dc.contributor.author | O'Toole, JF | |
dc.contributor.author | Hiller, KS | |
dc.contributor.author | Mueller, AM | |
dc.contributor.author | Beekmann, F | |
dc.contributor.author | Hoefele, J | |
dc.contributor.author | Landau, D | |
dc.contributor.author | Foreman, JW | |
dc.contributor.author | Goodship, JA | |
dc.contributor.author | Strachan, T | |
dc.contributor.author | Kispert, A | |
dc.contributor.author | Wolf, MT | |
dc.contributor.author | Gagnadoux, MF | |
dc.contributor.author | Nivet, H | |
dc.contributor.author | Antignac, C | |
dc.contributor.author | Walz, G | |
dc.contributor.author | Drummond, IA | |
dc.contributor.author | Benzing, T | |
dc.contributor.author | Hildebrandt, F | |
dc.coverage.spatial | Los Angeles, California | |
dc.date.accessioned | 2023-12-01T18:48:12Z | |
dc.date.available | 2023-12-01T18:48:12Z | |
dc.date.issued | 2003-08-01 | |
dc.identifier.issn | 1061-4036 | |
dc.identifier.issn | 1546-1718 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/12872123 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/191561 | en |
dc.description.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. | |
dc.format.medium | ||
dc.publisher | Springer Nature | |
dc.subject | Adaptor Proteins, Signal Transducing | |
dc.subject | Animals | |
dc.subject | Base Sequence | |
dc.subject | Body Patterning | |
dc.subject | Child | |
dc.subject | Cilia | |
dc.subject | Cytoskeletal Proteins | |
dc.subject | DNA | |
dc.subject | Female | |
dc.subject | Gene Targeting | |
dc.subject | Humans | |
dc.subject | Kidney Diseases, Cystic | |
dc.subject | Male | |
dc.subject | Membrane Proteins | |
dc.subject | Molecular Sequence Data | |
dc.subject | Mutation | |
dc.subject | Polycystic Kidney, Autosomal Recessive | |
dc.subject | Proteins | |
dc.subject | Situs Inversus | |
dc.subject | Transcription Factors | |
dc.subject | Tubulin | |
dc.subject | Zebrafish | |
dc.title | Mutations in Inversin cause Nephronophthisis Type 2, linking Cystic Kidney Disease to the Function of Primary Cilia and Left-Right Axis Determination | |
dc.type | Conference Paper | |
dc.identifier.pmid | 12872123 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/191561/2/78_Otto_NG_INVS_NPHP2_2003.pdf | |
dc.identifier.doi | 10.1038/ng1217 | |
dc.identifier.doi | https://dx.doi.org/10.7302/21845 | |
dc.identifier.source | Nature Genetics | |
dc.description.version | Published version | |
dc.date.updated | 2023-12-01T18:48:10Z | |
dc.identifier.orcid | 0000-0002-2387-9973 | |
dc.description.filedescription | Description of 78_Otto_NG_INVS_NPHP2_2003.pdf : Published version | |
dc.identifier.volume | 34 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 413 | |
dc.identifier.endpage | 420 | |
dc.identifier.name-orcid | Otto, EA; 0000-0002-2387-9973 | |
dc.identifier.name-orcid | Schermer, B | |
dc.identifier.name-orcid | Obara, T | |
dc.identifier.name-orcid | O'Toole, JF | |
dc.identifier.name-orcid | Hiller, KS | |
dc.identifier.name-orcid | Mueller, AM | |
dc.identifier.name-orcid | Beekmann, F | |
dc.identifier.name-orcid | Hoefele, J | |
dc.identifier.name-orcid | Landau, D | |
dc.identifier.name-orcid | Foreman, JW | |
dc.identifier.name-orcid | Goodship, JA | |
dc.identifier.name-orcid | Strachan, T | |
dc.identifier.name-orcid | Kispert, A | |
dc.identifier.name-orcid | Wolf, MT | |
dc.identifier.name-orcid | Gagnadoux, MF | |
dc.identifier.name-orcid | Nivet, H | |
dc.identifier.name-orcid | Antignac, C | |
dc.identifier.name-orcid | Walz, G | |
dc.identifier.name-orcid | Drummond, IA | |
dc.identifier.name-orcid | Benzing, T | |
dc.identifier.name-orcid | Hildebrandt, F | |
dc.working.doi | 10.7302/21845 | en |
dc.owningcollname | Pediatrics and Communicable Diseases, Department of |
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