title: Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress.
abstract: Glutathione 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 2.66±0.83 vs 1.13±0.20 mg/mmol for Gstk1(-/-) and wild-type (WT), respectively, P=0.001). 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.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra, Australia.
authors.forename: Anneke C
authors.initials: AC
authors.lastname: Blackburn
authors.forename: Marjorie
authors.initials: M
authors.lastname: Coggan
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Shield
authors.forename: Jean
authors.initials: J
authors.lastname: Cappello
authors.forename: Angelo
authors.initials: A
authors.lastname: Theodoratos
authors.forename: Tracy P
authors.initials: TP
authors.lastname: Murray
authors.forename: Melissa
authors.initials: M
authors.lastname: Rooke
authors.forename: Claire Z
authors.initials: CZ
authors.lastname: Larter
authors.forename: Mark E
authors.initials: ME
authors.lastname: Koina
authors.forename: Jane E
authors.initials: JE
authors.lastname: Dahlstrom
authors.forename: Klaus I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: Philip G
authors.initials: PG
authors.lastname: Board
mesh_terms: D000419:Albuminuria / Q000209:etiology; D000818:Animals; D001774:Blood Chemical Analysis; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology*; D005982:Glutathione Transferase / Q000172:deficiency*; D007150:Immunohistochemistry; D007668:Kidney / Q000648:ultrastructure; D008099:Liver / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000502:physiology; D016482:Urinalysis
chemical_list: D005982:Glutathione Transferase; C568627:glutathione transferase kappa, mouse