A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08-16

AUTHORS

John K McCooke, Rudi Appels, Roberto A Barrero, Alice Ding, Justyna E Ozimek-Kulik, Mathew I Bellgard, Grant Morahan, Jacqueline K Phillips

ABSTRACT

BackgroundNephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat.ResultsIn this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation.ConclusionsWhen assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins. More... »

PAGES

393

References to SciGraph publications

  • 2002-02-04. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein in NATURE GENETICS
  • 2010-07-22. Nephronophthisis in PEDIATRIC NEPHROLOGY
  • 1999-08-26. Primer3 on the WWW for General Users and for Biologist Programmers in BIOINFORMATICS METHODS AND PROTOCOLS
  • 2008-01-09. Defects in ciliary localization of Nek8 is associated with cystogenesis in PEDIATRIC NEPHROLOGY
  • 2008-07-08. Nephronophthisis in PEDIATRIC NEPHROLOGY
  • 2001-09-20. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the β-catenin gene in ONCOGENE
  • 2006-02-19. Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polarity and Hedgehog signaling in NATURE GENETICS
  • 2008-11-21. An interrupted beta-propeller and protein disorder: structural bioinformatics insights into the N-terminus of alsin in JOURNAL OF MOLECULAR MODELING
  • 2009-02-26. Protein structure prediction on the Web: a case study using the Phyre server in NATURE PROTOCOLS
  • 2005-12. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? in NATURE REVIEWS GENETICS
  • 2002-04-05. An arginine to cysteine252 mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events in DIABETOLOGIA
  • 2007-11. When cilia go bad: cilia defects and ciliopathies in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 1998-03. The 1.7 Å crystal structure of the regulator of chromosome condensation (RCC1) reveals a seven-bladed propeller in NATURE
  • 2007-08-29. Mitotic regulation by NIMA-related kinases in CELL DIVISION
  • 2009-03-04. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome in GENOME BIOLOGY
  • 2001-12. Map Manager QTX, cross-platform software for genetic mapping in MAMMALIAN GENOME
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/1471-2164-13-393

    DOI

    http://dx.doi.org/10.1186/1471-2164-13-393

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1050589101

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/22899815


    Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
    Incoming Citations Browse incoming citations for this publication using opencitations.net

    JSON-LD is the canonical representation for SciGraph data.

    TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

    [
      {
        "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
        "about": [
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Biological Sciences", 
            "type": "DefinedTerm"
          }, 
          {
            "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0604", 
            "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
            "name": "Genetics", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Amino Acid Sequence", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Animals", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Chromosomes", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Cilia", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Humans", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Kidney Diseases, Cystic", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mice", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Molecular Sequence Data", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Mutation", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "NIMA-Related Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Polymorphism, Single Nucleotide", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Serine-Threonine Kinases", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Protein Structure, Tertiary", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Quantitative Trait Loci", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Rats", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Alignment", 
            "type": "DefinedTerm"
          }, 
          {
            "inDefinedTermSet": "https://www.nlm.nih.gov/mesh/", 
            "name": "Sequence Analysis, DNA", 
            "type": "DefinedTerm"
          }
        ], 
        "author": [
          {
            "affiliation": {
              "alternateName": "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1025.6", 
              "name": [
                "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "McCooke", 
            "givenName": "John K", 
            "id": "sg:person.0732327045.66", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732327045.66"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1025.6", 
              "name": [
                "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Appels", 
            "givenName": "Rudi", 
            "id": "sg:person.01117454167.49", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117454167.49"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1025.6", 
              "name": [
                "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Barrero", 
            "givenName": "Roberto A", 
            "id": "sg:person.0633457135.09", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633457135.09"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1004.5", 
              "name": [
                "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ding", 
            "givenName": "Alice", 
            "id": "sg:person.01246404671.03", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01246404671.03"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1004.5", 
              "name": [
                "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Ozimek-Kulik", 
            "givenName": "Justyna E", 
            "id": "sg:person.01362633271.00", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362633271.00"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1025.6", 
              "name": [
                "Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Bellgard", 
            "givenName": "Mathew I", 
            "id": "sg:person.01233702567.15", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233702567.15"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "The Western Australian Institute for Medical Research, University of Western Australia, 6000, Perth, WA, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1012.2", 
              "name": [
                "The Western Australian Institute for Medical Research, University of Western Australia, 6000, Perth, WA, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Morahan", 
            "givenName": "Grant", 
            "id": "sg:person.01040420150.94", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01040420150.94"
            ], 
            "type": "Person"
          }, 
          {
            "affiliation": {
              "alternateName": "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia", 
              "id": "http://www.grid.ac/institutes/grid.1004.5", 
              "name": [
                "Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia"
              ], 
              "type": "Organization"
            }, 
            "familyName": "Phillips", 
            "givenName": "Jacqueline K", 
            "id": "sg:person.0633201277.70", 
            "sameAs": [
              "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633201277.70"
            ], 
            "type": "Person"
          }
        ], 
        "citation": [
          {
            "id": "sg:pub.10.1186/gb-2009-10-3-r25", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1049583368", 
              "https://doi.org/10.1186/gb-2009-10-3-r25"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/32204", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002348956", 
              "https://doi.org/10.1038/32204"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng833", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029076315", 
              "https://doi.org/10.1038/ng833"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00894-008-0381-1", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1004843273", 
              "https://doi.org/10.1007/s00894-008-0381-1"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00467-010-1585-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1041953917", 
              "https://doi.org/10.1007/s00467-010-1585-z"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/ng1753", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1012389040", 
              "https://doi.org/10.1038/ng1753"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00335-001-1016-3", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1032730610", 
              "https://doi.org/10.1007/s00335-001-1016-3"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrm2278", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1053367126", 
              "https://doi.org/10.1038/nrm2278"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00467-007-0692-y", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1037766476", 
              "https://doi.org/10.1007/s00467-007-0692-y"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/sj.onc.1204825", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1001417393", 
              "https://doi.org/10.1038/sj.onc.1204825"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nprot.2009.2", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1029454980", 
              "https://doi.org/10.1038/nprot.2009.2"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00125-002-0798-5", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1010780145", 
              "https://doi.org/10.1007/s00125-002-0798-5"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1186/1747-1028-2-25", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1002811923", 
              "https://doi.org/10.1186/1747-1028-2-25"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1038/nrg1727", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048662366", 
              "https://doi.org/10.1038/nrg1727"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1385/1-59259-192-2:365", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1023668922", 
              "https://doi.org/10.1385/1-59259-192-2:365"
            ], 
            "type": "CreativeWork"
          }, 
          {
            "id": "sg:pub.10.1007/s00467-008-0840-z", 
            "sameAs": [
              "https://app.dimensions.ai/details/publication/pub.1048563628", 
              "https://doi.org/10.1007/s00467-008-0840-z"
            ], 
            "type": "CreativeWork"
          }
        ], 
        "datePublished": "2012-08-16", 
        "datePublishedReg": "2012-08-16", 
        "description": "BackgroundNephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat.ResultsIn this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation.ConclusionsWhen assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.", 
        "genre": "article", 
        "id": "sg:pub.10.1186/1471-2164-13-393", 
        "isAccessibleForFree": true, 
        "isPartOf": [
          {
            "id": "sg:journal.1023790", 
            "issn": [
              "1471-2164"
            ], 
            "name": "BMC Genomics", 
            "publisher": "Springer Nature", 
            "type": "Periodical"
          }, 
          {
            "issueNumber": "1", 
            "type": "PublicationIssue"
          }, 
          {
            "type": "PublicationVolume", 
            "volumeNumber": "13"
          }
        ], 
        "keywords": [
          "RCC1 domain", 
          "cystic kidney disease", 
          "quantitative trait locus (QTL) analysis", 
          "chromosome condensation 1", 
          "beta-propeller structure", 
          "human chromosome 17", 
          "genome capture", 
          "region syntenic", 
          "kidney epithelial cells", 
          "Nek8 gene", 
          "cilia proteins", 
          "loss of function", 
          "chromosome 10q25", 
          "autosomal recessive phenotype", 
          "mitosis gene", 
          "repeat motifs", 
          "next-generation sequencing", 
          "novel model system", 
          "condensation 1", 
          "primary cilia", 
          "recessive phenotype", 
          "locus analysis", 
          "comparable phenotypes", 
          "common genetic cause", 
          "chromosome 17", 
          "genes", 
          "protein", 
          "long cilia", 
          "propeller structure", 
          "mutations", 
          "genetic cause", 
          "NPHP", 
          "epithelial cells", 
          "model system", 
          "different mutations", 
          "novel mutations", 
          "cilia", 
          "mouse 11", 
          "kidney disease", 
          "phenotype", 
          "like region", 
          "syntenic", 
          "NEK8", 
          "domain", 
          "Lewis polycystic kidney rats", 
          "localises", 
          "fluorescence immunohistochemistry", 
          "progressive renal failure", 
          "NIMA", 
          "regulator", 
          "sequencing", 
          "polycystic kidney (PCK) rat", 
          "motif", 
          "nephronophthisis", 
          "LPK rats", 
          "kidney rats", 
          "renal failure", 
          "region", 
          "cells", 
          "young adults", 
          "disease", 
          "localisation", 
          "rats", 
          "electron microscopy", 
          "substitution", 
          "structure", 
          "cause", 
          "function", 
          "microscopy", 
          "portion", 
          "immunohistochemistry", 
          "ResultsIn", 
          "loss", 
          "study", 
          "adults", 
          "capture", 
          "children", 
          "analysis", 
          "link", 
          "ConclusionsWhen", 
          "failure", 
          "results", 
          "system"
        ], 
        "name": "A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8", 
        "pagination": "393", 
        "productId": [
          {
            "name": "dimensions_id", 
            "type": "PropertyValue", 
            "value": [
              "pub.1050589101"
            ]
          }, 
          {
            "name": "doi", 
            "type": "PropertyValue", 
            "value": [
              "10.1186/1471-2164-13-393"
            ]
          }, 
          {
            "name": "pubmed_id", 
            "type": "PropertyValue", 
            "value": [
              "22899815"
            ]
          }
        ], 
        "sameAs": [
          "https://doi.org/10.1186/1471-2164-13-393", 
          "https://app.dimensions.ai/details/publication/pub.1050589101"
        ], 
        "sdDataset": "articles", 
        "sdDatePublished": "2022-12-01T06:30", 
        "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
        "sdPublisher": {
          "name": "Springer Nature - SN SciGraph project", 
          "type": "Organization"
        }, 
        "sdSource": "s3://com-springernature-scigraph/baseset/20221201/entities/gbq_results/article/article_571.jsonl", 
        "type": "ScholarlyArticle", 
        "url": "https://doi.org/10.1186/1471-2164-13-393"
      }
    ]
     

    Download the RDF metadata as:  json-ld nt turtle xml License info

    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular format for linked data which is fully compatible with JSON.

    curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-13-393'

    N-Triples is a line-based linked data format ideal for batch operations.

    curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-13-393'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-13-393'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-13-393'


     

    This table displays all metadata directly associated to this object as RDF triples.

    330 TRIPLES      21 PREDICATES      141 URIs      117 LITERALS      24 BLANK NODES

    Subject Predicate Object
    1 sg:pub.10.1186/1471-2164-13-393 schema:about N11257723a7984aa4927c71704f9e9de3
    2 N22aaada520d446d5a5b91215509a23de
    3 N3db22f6be65f4ff7b01aa07825b73407
    4 N470211d664ff435db255a541037d7e61
    5 N4cf488e4e136427381c68fa1b26ef3ac
    6 N6f6c3e79af7849d8b73d0d164e46f97e
    7 N7ceab633a8fa4aa3af4d451cd9caf7b6
    8 N8d3a615b20f146348edddb84fe39131a
    9 N904f7e0fc4854043b9613cfde463b01e
    10 Na06bb75329c8468fb738e2fcc36f3850
    11 Naa6f986b49264f6790f5a44a490483a3
    12 Nac215fb239774bd59c228888cfaaefc7
    13 Nc7cbe18030bc4018bf1c87700a5a623f
    14 Ncdb8234757a94ecea0c97be7b459e1a4
    15 Nda172827f11f4711a8d1c54fd7e36e29
    16 Ne14c7499e3da442e920b6b906f25d878
    17 Nfad3cc35762d4331ba53542800617210
    18 anzsrc-for:06
    19 anzsrc-for:0604
    20 schema:author N7a074dad515543afa79e8a10a44c9a27
    21 schema:citation sg:pub.10.1007/s00125-002-0798-5
    22 sg:pub.10.1007/s00335-001-1016-3
    23 sg:pub.10.1007/s00467-007-0692-y
    24 sg:pub.10.1007/s00467-008-0840-z
    25 sg:pub.10.1007/s00467-010-1585-z
    26 sg:pub.10.1007/s00894-008-0381-1
    27 sg:pub.10.1038/32204
    28 sg:pub.10.1038/ng1753
    29 sg:pub.10.1038/ng833
    30 sg:pub.10.1038/nprot.2009.2
    31 sg:pub.10.1038/nrg1727
    32 sg:pub.10.1038/nrm2278
    33 sg:pub.10.1038/sj.onc.1204825
    34 sg:pub.10.1186/1747-1028-2-25
    35 sg:pub.10.1186/gb-2009-10-3-r25
    36 sg:pub.10.1385/1-59259-192-2:365
    37 schema:datePublished 2012-08-16
    38 schema:datePublishedReg 2012-08-16
    39 schema:description BackgroundNephronophthisis (NPHP) as a cause of cystic kidney disease is the most common genetic cause of progressive renal failure in children and young adults. NPHP is characterized by abnormal and/or loss of function of proteins associated with primary cilia. Previously, we characterized an autosomal recessive phenotype of cystic kidney disease in the Lewis Polycystic Kidney (LPK) rat.ResultsIn this study, quantitative trait locus analysis was used to define a ~1.6Mbp region on rat chromosome 10q25 harbouring the lpk mutation. Targeted genome capture and next-generation sequencing of this region identified a non-synonymous mutation R650C in the NIMA (never in mitosis gene a)- related kinase 8 ( Nek8) gene. This is a novel Nek8 mutation that occurs within the regulator of chromosome condensation 1 (RCC1)-like region of the protein. Specifically, the R650C substitution is located within a G[QRC]LG repeat motif of the predicted seven bladed beta-propeller structure of the RCC1 domain. The rat Nek8 gene is located in a region syntenic to portions of human chromosome 17 and mouse 11. Scanning electron microscopy confirmed abnormally long cilia on LPK kidney epithelial cells, and fluorescence immunohistochemistry for Nek8 protein revealed altered cilia localisation.ConclusionsWhen assessed relative to other Nek8 NPHP mutations, our results indicate the whole propeller structure of the RCC1 domain is important, as the different mutations cause comparable phenotypes. This study establishes the LPK rat as a novel model system for NPHP and further consolidates the link between cystic kidney disease and cilia proteins.
    40 schema:genre article
    41 schema:isAccessibleForFree true
    42 schema:isPartOf N2e017dab62144678aa1a717aaf01f3ce
    43 N8b3c670a4f204566b064e2f734dd5f70
    44 sg:journal.1023790
    45 schema:keywords ConclusionsWhen
    46 LPK rats
    47 Lewis polycystic kidney rats
    48 NEK8
    49 NIMA
    50 NPHP
    51 Nek8 gene
    52 RCC1 domain
    53 ResultsIn
    54 adults
    55 analysis
    56 autosomal recessive phenotype
    57 beta-propeller structure
    58 capture
    59 cause
    60 cells
    61 children
    62 chromosome 10q25
    63 chromosome 17
    64 chromosome condensation 1
    65 cilia
    66 cilia proteins
    67 common genetic cause
    68 comparable phenotypes
    69 condensation 1
    70 cystic kidney disease
    71 different mutations
    72 disease
    73 domain
    74 electron microscopy
    75 epithelial cells
    76 failure
    77 fluorescence immunohistochemistry
    78 function
    79 genes
    80 genetic cause
    81 genome capture
    82 human chromosome 17
    83 immunohistochemistry
    84 kidney disease
    85 kidney epithelial cells
    86 kidney rats
    87 like region
    88 link
    89 localisation
    90 localises
    91 locus analysis
    92 long cilia
    93 loss
    94 loss of function
    95 microscopy
    96 mitosis gene
    97 model system
    98 motif
    99 mouse 11
    100 mutations
    101 nephronophthisis
    102 next-generation sequencing
    103 novel model system
    104 novel mutations
    105 phenotype
    106 polycystic kidney (PCK) rat
    107 portion
    108 primary cilia
    109 progressive renal failure
    110 propeller structure
    111 protein
    112 quantitative trait locus (QTL) analysis
    113 rats
    114 recessive phenotype
    115 region
    116 region syntenic
    117 regulator
    118 renal failure
    119 repeat motifs
    120 results
    121 sequencing
    122 structure
    123 study
    124 substitution
    125 syntenic
    126 system
    127 young adults
    128 schema:name A novel mutation causing nephronophthisis in the Lewis polycystic kidney rat localises to a conserved RCC1 domain in Nek8
    129 schema:pagination 393
    130 schema:productId N2776cabcf10642b183ebaba60a2abc91
    131 N3ca6f1b0fad2463f9d71ce2b46f6e518
    132 Nedf4f8ccb77d4271b5740fcc1ccb9b8f
    133 schema:sameAs https://app.dimensions.ai/details/publication/pub.1050589101
    134 https://doi.org/10.1186/1471-2164-13-393
    135 schema:sdDatePublished 2022-12-01T06:30
    136 schema:sdLicense https://scigraph.springernature.com/explorer/license/
    137 schema:sdPublisher Nd2a0c02178d8499ba3b803f756c53929
    138 schema:url https://doi.org/10.1186/1471-2164-13-393
    139 sgo:license sg:explorer/license/
    140 sgo:sdDataset articles
    141 rdf:type schema:ScholarlyArticle
    142 N071d792dd2184c8c83602f257f9ee912 rdf:first sg:person.01246404671.03
    143 rdf:rest Na0310ab8a085429d80d799bb18def5db
    144 N11257723a7984aa4927c71704f9e9de3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    145 schema:name Quantitative Trait Loci
    146 rdf:type schema:DefinedTerm
    147 N16147b58d3034027abfe7d71ae32a2ab rdf:first sg:person.01233702567.15
    148 rdf:rest N36a9383c6ec3400684c2d507e936a0bd
    149 N192885ddcd8241efb137f3af9f21af43 rdf:first sg:person.0633457135.09
    150 rdf:rest N071d792dd2184c8c83602f257f9ee912
    151 N22aaada520d446d5a5b91215509a23de schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    152 schema:name Animals
    153 rdf:type schema:DefinedTerm
    154 N2776cabcf10642b183ebaba60a2abc91 schema:name doi
    155 schema:value 10.1186/1471-2164-13-393
    156 rdf:type schema:PropertyValue
    157 N2e017dab62144678aa1a717aaf01f3ce schema:volumeNumber 13
    158 rdf:type schema:PublicationVolume
    159 N36a9383c6ec3400684c2d507e936a0bd rdf:first sg:person.01040420150.94
    160 rdf:rest Ne0c4c033c3744fa4ae810ba218a9811f
    161 N3ca6f1b0fad2463f9d71ce2b46f6e518 schema:name pubmed_id
    162 schema:value 22899815
    163 rdf:type schema:PropertyValue
    164 N3db22f6be65f4ff7b01aa07825b73407 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    165 schema:name Polymorphism, Single Nucleotide
    166 rdf:type schema:DefinedTerm
    167 N470211d664ff435db255a541037d7e61 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    168 schema:name Amino Acid Sequence
    169 rdf:type schema:DefinedTerm
    170 N4cf488e4e136427381c68fa1b26ef3ac schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    171 schema:name Protein Structure, Tertiary
    172 rdf:type schema:DefinedTerm
    173 N6f6c3e79af7849d8b73d0d164e46f97e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    174 schema:name Mutation
    175 rdf:type schema:DefinedTerm
    176 N7a074dad515543afa79e8a10a44c9a27 rdf:first sg:person.0732327045.66
    177 rdf:rest N84350cf4234446da9e2c8ab55c96bb92
    178 N7ceab633a8fa4aa3af4d451cd9caf7b6 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    179 schema:name Cilia
    180 rdf:type schema:DefinedTerm
    181 N84350cf4234446da9e2c8ab55c96bb92 rdf:first sg:person.01117454167.49
    182 rdf:rest N192885ddcd8241efb137f3af9f21af43
    183 N8b3c670a4f204566b064e2f734dd5f70 schema:issueNumber 1
    184 rdf:type schema:PublicationIssue
    185 N8d3a615b20f146348edddb84fe39131a schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    186 schema:name Sequence Analysis, DNA
    187 rdf:type schema:DefinedTerm
    188 N904f7e0fc4854043b9613cfde463b01e schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    189 schema:name Rats
    190 rdf:type schema:DefinedTerm
    191 Na0310ab8a085429d80d799bb18def5db rdf:first sg:person.01362633271.00
    192 rdf:rest N16147b58d3034027abfe7d71ae32a2ab
    193 Na06bb75329c8468fb738e2fcc36f3850 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    194 schema:name NIMA-Related Kinases
    195 rdf:type schema:DefinedTerm
    196 Naa6f986b49264f6790f5a44a490483a3 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    197 schema:name Sequence Alignment
    198 rdf:type schema:DefinedTerm
    199 Nac215fb239774bd59c228888cfaaefc7 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    200 schema:name Molecular Sequence Data
    201 rdf:type schema:DefinedTerm
    202 Nc7cbe18030bc4018bf1c87700a5a623f schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    203 schema:name Protein Serine-Threonine Kinases
    204 rdf:type schema:DefinedTerm
    205 Ncdb8234757a94ecea0c97be7b459e1a4 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    206 schema:name Mice
    207 rdf:type schema:DefinedTerm
    208 Nd2a0c02178d8499ba3b803f756c53929 schema:name Springer Nature - SN SciGraph project
    209 rdf:type schema:Organization
    210 Nda172827f11f4711a8d1c54fd7e36e29 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    211 schema:name Humans
    212 rdf:type schema:DefinedTerm
    213 Ne0c4c033c3744fa4ae810ba218a9811f rdf:first sg:person.0633201277.70
    214 rdf:rest rdf:nil
    215 Ne14c7499e3da442e920b6b906f25d878 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    216 schema:name Kidney Diseases, Cystic
    217 rdf:type schema:DefinedTerm
    218 Nedf4f8ccb77d4271b5740fcc1ccb9b8f schema:name dimensions_id
    219 schema:value pub.1050589101
    220 rdf:type schema:PropertyValue
    221 Nfad3cc35762d4331ba53542800617210 schema:inDefinedTermSet https://www.nlm.nih.gov/mesh/
    222 schema:name Chromosomes
    223 rdf:type schema:DefinedTerm
    224 anzsrc-for:06 schema:inDefinedTermSet anzsrc-for:
    225 schema:name Biological Sciences
    226 rdf:type schema:DefinedTerm
    227 anzsrc-for:0604 schema:inDefinedTermSet anzsrc-for:
    228 schema:name Genetics
    229 rdf:type schema:DefinedTerm
    230 sg:journal.1023790 schema:issn 1471-2164
    231 schema:name BMC Genomics
    232 schema:publisher Springer Nature
    233 rdf:type schema:Periodical
    234 sg:person.01040420150.94 schema:affiliation grid-institutes:grid.1012.2
    235 schema:familyName Morahan
    236 schema:givenName Grant
    237 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01040420150.94
    238 rdf:type schema:Person
    239 sg:person.01117454167.49 schema:affiliation grid-institutes:grid.1025.6
    240 schema:familyName Appels
    241 schema:givenName Rudi
    242 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01117454167.49
    243 rdf:type schema:Person
    244 sg:person.01233702567.15 schema:affiliation grid-institutes:grid.1025.6
    245 schema:familyName Bellgard
    246 schema:givenName Mathew I
    247 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233702567.15
    248 rdf:type schema:Person
    249 sg:person.01246404671.03 schema:affiliation grid-institutes:grid.1004.5
    250 schema:familyName Ding
    251 schema:givenName Alice
    252 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01246404671.03
    253 rdf:type schema:Person
    254 sg:person.01362633271.00 schema:affiliation grid-institutes:grid.1004.5
    255 schema:familyName Ozimek-Kulik
    256 schema:givenName Justyna E
    257 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01362633271.00
    258 rdf:type schema:Person
    259 sg:person.0633201277.70 schema:affiliation grid-institutes:grid.1004.5
    260 schema:familyName Phillips
    261 schema:givenName Jacqueline K
    262 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633201277.70
    263 rdf:type schema:Person
    264 sg:person.0633457135.09 schema:affiliation grid-institutes:grid.1025.6
    265 schema:familyName Barrero
    266 schema:givenName Roberto A
    267 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0633457135.09
    268 rdf:type schema:Person
    269 sg:person.0732327045.66 schema:affiliation grid-institutes:grid.1025.6
    270 schema:familyName McCooke
    271 schema:givenName John K
    272 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0732327045.66
    273 rdf:type schema:Person
    274 sg:pub.10.1007/s00125-002-0798-5 schema:sameAs https://app.dimensions.ai/details/publication/pub.1010780145
    275 https://doi.org/10.1007/s00125-002-0798-5
    276 rdf:type schema:CreativeWork
    277 sg:pub.10.1007/s00335-001-1016-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1032730610
    278 https://doi.org/10.1007/s00335-001-1016-3
    279 rdf:type schema:CreativeWork
    280 sg:pub.10.1007/s00467-007-0692-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1037766476
    281 https://doi.org/10.1007/s00467-007-0692-y
    282 rdf:type schema:CreativeWork
    283 sg:pub.10.1007/s00467-008-0840-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1048563628
    284 https://doi.org/10.1007/s00467-008-0840-z
    285 rdf:type schema:CreativeWork
    286 sg:pub.10.1007/s00467-010-1585-z schema:sameAs https://app.dimensions.ai/details/publication/pub.1041953917
    287 https://doi.org/10.1007/s00467-010-1585-z
    288 rdf:type schema:CreativeWork
    289 sg:pub.10.1007/s00894-008-0381-1 schema:sameAs https://app.dimensions.ai/details/publication/pub.1004843273
    290 https://doi.org/10.1007/s00894-008-0381-1
    291 rdf:type schema:CreativeWork
    292 sg:pub.10.1038/32204 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002348956
    293 https://doi.org/10.1038/32204
    294 rdf:type schema:CreativeWork
    295 sg:pub.10.1038/ng1753 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012389040
    296 https://doi.org/10.1038/ng1753
    297 rdf:type schema:CreativeWork
    298 sg:pub.10.1038/ng833 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029076315
    299 https://doi.org/10.1038/ng833
    300 rdf:type schema:CreativeWork
    301 sg:pub.10.1038/nprot.2009.2 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029454980
    302 https://doi.org/10.1038/nprot.2009.2
    303 rdf:type schema:CreativeWork
    304 sg:pub.10.1038/nrg1727 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048662366
    305 https://doi.org/10.1038/nrg1727
    306 rdf:type schema:CreativeWork
    307 sg:pub.10.1038/nrm2278 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053367126
    308 https://doi.org/10.1038/nrm2278
    309 rdf:type schema:CreativeWork
    310 sg:pub.10.1038/sj.onc.1204825 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001417393
    311 https://doi.org/10.1038/sj.onc.1204825
    312 rdf:type schema:CreativeWork
    313 sg:pub.10.1186/1747-1028-2-25 schema:sameAs https://app.dimensions.ai/details/publication/pub.1002811923
    314 https://doi.org/10.1186/1747-1028-2-25
    315 rdf:type schema:CreativeWork
    316 sg:pub.10.1186/gb-2009-10-3-r25 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049583368
    317 https://doi.org/10.1186/gb-2009-10-3-r25
    318 rdf:type schema:CreativeWork
    319 sg:pub.10.1385/1-59259-192-2:365 schema:sameAs https://app.dimensions.ai/details/publication/pub.1023668922
    320 https://doi.org/10.1385/1-59259-192-2:365
    321 rdf:type schema:CreativeWork
    322 grid-institutes:grid.1004.5 schema:alternateName Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia
    323 schema:name Australian School of Advanced Medicine, Macquarie University, 2109, Sydney, NSW, Australia
    324 rdf:type schema:Organization
    325 grid-institutes:grid.1012.2 schema:alternateName The Western Australian Institute for Medical Research, University of Western Australia, 6000, Perth, WA, Australia
    326 schema:name The Western Australian Institute for Medical Research, University of Western Australia, 6000, Perth, WA, Australia
    327 rdf:type schema:Organization
    328 grid-institutes:grid.1025.6 schema:alternateName Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia
    329 schema:name Centre for Comparative Genomics, Murdoch University, 6150, Perth, WA, Australia
    330 rdf:type schema:Organization
     




    Preview window. Press ESC to close (or click here)


    ...