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Next-generation sequencing to dissect hereditary nephrotic syndrome in mice identifies a hypomorphic mutation in Lamb2 and models Pierson's syndrome

Bull, Katherine R; Mason, Thomas; Rimmer, Andrew J.; Crockford, Tanya; Silver, Karlee; Bouriez-Jones, Tiphaine; Hough, Tertius; Chaudhry, Shirine; Roberts, Ian S; Goodnow, Christopher; Cornall, Richard J

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The study of mutations causing the steroid-resistant nephrotic syndrome in children has greatly advanced our understanding of the kidney filtration barrier. In particular, these genetic variants have illuminated the roles of the podocyte, glomerular basement membrane and endothelial cell in glomerular filtration. However, in a significant number of familial and early onset cases, an underlying mutation cannot be identified, indicating that there are likely to be multiple unknown genes with...[Show more]

dc.contributor.authorBull, Katherine R
dc.contributor.authorMason, Thomas
dc.contributor.authorRimmer, Andrew J.
dc.contributor.authorCrockford, Tanya
dc.contributor.authorSilver, Karlee
dc.contributor.authorBouriez-Jones, Tiphaine
dc.contributor.authorHough, Tertius
dc.contributor.authorChaudhry, Shirine
dc.contributor.authorRoberts, Ian S
dc.contributor.authorGoodnow, Christopher
dc.contributor.authorCornall, Richard J
dc.date.accessioned2015-12-10T22:12:38Z
dc.identifier.issn0022-3417
dc.identifier.urihttp://hdl.handle.net/1885/49751
dc.description.abstractThe study of mutations causing the steroid-resistant nephrotic syndrome in children has greatly advanced our understanding of the kidney filtration barrier. In particular, these genetic variants have illuminated the roles of the podocyte, glomerular basement membrane and endothelial cell in glomerular filtration. However, in a significant number of familial and early onset cases, an underlying mutation cannot be identified, indicating that there are likely to be multiple unknown genes with roles in glomerular permeability. We now show how the combination of N-ethyl-N-nitrosourea mutagenesis and next-generation sequencing could be used to identify the range of mutations affecting these pathways. Using this approach, we isolated a novel mouse strain with a viable nephrotic phenotype and used whole-genome sequencing to isolate a causative hypomorphic mutation in Lamb2. This discovery generated a model for one part of the spectrum of human Pierson's syndrome and provides a powerful proof of principle for accelerating gene discovery and improving our understanding of inherited forms of renal disease.
dc.publisherJohn Wiley & Sons Inc
dc.sourceJournal of Pathology
dc.titleNext-generation sequencing to dissect hereditary nephrotic syndrome in mice identifies a hypomorphic mutation in Lamb2 and models Pierson's syndrome
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume233
dc.date.issued2014
local.identifier.absfor110799 - Immunology not elsewhere classified
local.identifier.ariespublicationu6800332xPUB191
local.type.statusPublished Version
local.contributor.affiliationBull, Katherine R, University of Oxford
local.contributor.affiliationMason, Thomas, Oxford University
local.contributor.affiliationRimmer, Andrew J., Oxford University
local.contributor.affiliationCrockford, Tanya, University of Oxford
local.contributor.affiliationSilver, Karlee, University of Oxford
local.contributor.affiliationBouriez-Jones, Tiphaine, Oxford University
local.contributor.affiliationHough, Tertius, MRC Mammalian Genetics Unit
local.contributor.affiliationChaudhry, Shirine, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRoberts, Ian S, John Radcliffe Hospital
local.contributor.affiliationGoodnow, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCornall, Richard J, Oxford University
local.description.embargo2037-12-31
local.bibliographicCitation.issue1
local.bibliographicCitation.startpage18
local.bibliographicCitation.lastpage26
local.identifier.doi10.1002/path.4308
dc.date.updated2015-12-09T07:54:58Z
local.identifier.scopusID2-s2.0-84898426390
local.identifier.thomsonID000334376500004
CollectionsANU Research Publications

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