Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress

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dc.contributor.authorBlackburn, Annekeen_AU
dc.contributor.authorCoggan, Marjorieen_AU
dc.contributor.authorShield, Alisonen_AU
dc.contributor.authorCappello, Jeanen_AU
dc.contributor.authorTheodoratos, Angeloen_AU
dc.contributor.authorMurray, Tracyen_AU
dc.contributor.authorRooke, Melissaen_AU
dc.contributor.authorLarter, Claireen_AU
dc.contributor.authorKoina, Marken_AU
dc.contributor.authorMatthaei, Klausen_AU
dc.contributor.authorBoard, Philipen_AU
dc.contributor.authorDahlstrom, Janeen_AU
dc.date.accessioned2015-12-07T22:33:38Z
dc.date.issued2011
dc.date.updated2016-02-24T11:31:43Z
dc.description.abstractGlutathione transferase kappa (GSTK1-1) is a highly conserved, mitochondrial enzyme potentially involved in redox reactions. GSTK1-1-deficient mice were generated to further study the enzyme's biological role. Reduced and total glutathione levels in liver and kidney were unchanged by GSTK1-1 deficiency and NADPH quinone oxidoreductase 1 expression was not elevated indicating that there is no general underlying oxidative stress in Gstk1 / mice. Electron microscopy of liver and kidney showed no changes in mitochondrial morphology with GSTK1-1 deficiency. The death of a number of Gstk1 / males with urinary tract problems prompted close examination of the kidneys. Electron microscopy revealed glomerular basement membrane changes at 3 months, accompanied by detectable microalbuminuria in male mice (albumin:creatinine ratio of 2.660.83 vs 1.130.20 mg/mmol for Gstk1 / and wild-type (WT), respectively, P0.001). This was followed by significant foot process effacement (40-55% vs 10% for Gstk1 / and WT, respectively) at 6 months of age in all Gstk1 / mice examined. Kidney tubules were ultrastructurally normal. Compared with human disease, the Gstk1 / kidneys show changes seen in glomerulopathies causing nephrotic syndrome. Gstk1 / mice may offer insights into the early development of glomerular nephropathies.
dc.identifier.issn0023-6837
dc.identifier.urihttp://hdl.handle.net/1885/23375
dc.publisherLippincott Williams & Wilkins
dc.sourceLaboratory Investigation
dc.subjectKeywords: albumin; creatinine; glutathione transferase; glutathione transferase kappa 1; lipid; unclassified drug; animal experiment; animal model; animal tissue; article; blood analysis; body weight; cell structure; electron microscopy; enzyme deficiency; glomerul glomerular nephropathy; glutathione transferase kappa; GSTK1-1 deficiency; knockout mice; mitochondria
dc.titleGlutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress
dc.typeJournal article
local.bibliographicCitation.issue11
local.bibliographicCitation.lastpage1583
local.bibliographicCitation.startpage1572
local.contributor.affiliationBlackburn, Anneke, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCoggan, Marjorie, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationShield, Alison, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationCappello, Jean, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationTheodoratos, Angelo, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMurray, Tracy, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationRooke, Melissa, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationLarter, Claire, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationKoina, Mark, The Canberra Hospital
local.contributor.affiliationDahlstrom, Jane, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationMatthaei, Klaus, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationBoard, Philip, College of Medicine, Biology and Environment, ANU
local.contributor.authoremailu4048450@anu.edu.au
local.contributor.authoruidBlackburn, Anneke, u4048450
local.contributor.authoruidCoggan, Marjorie, u7400157
local.contributor.authoruidShield, Alison, u4105072
local.contributor.authoruidCappello, Jean, u9601131
local.contributor.authoruidTheodoratos, Angelo, u4036935
local.contributor.authoruidMurray, Tracy, u4053726
local.contributor.authoruidRooke, Melissa, u4187567
local.contributor.authoruidLarter, Claire, u4367140
local.contributor.authoruidDahlstrom, Jane, u1856057
local.contributor.authoruidMatthaei, Klaus, u8200697
local.contributor.authoruidBoard, Philip, u7701651
local.description.embargo2037-12-31
local.description.notesImported from ARIES
local.identifier.absfor110316 - Pathology
local.identifier.ariespublicationu4971216xPUB26
local.identifier.citationvolume91
local.identifier.doi10.1038/labinvest.2011.107
local.identifier.scopusID2-s2.0-80155151944
local.identifier.thomsonID000296603400003
local.identifier.uidSubmittedByu4971216
local.type.statusPublished Version

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