| First Author | Blackburn AC | Year | 2011 |
| Journal | Lab Invest | Volume | 91 |
| Issue | 11 | Pages | 1572-83 |
| PubMed ID | 21826057 | Mgi Jnum | J:177201 |
| Mgi Id | MGI:5294488 | Doi | 10.1038/labinvest.2011.107 |
| Citation | Blackburn AC, et al. (2011) Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress. Lab Invest 91(11):1572-83 |
| abstractText | 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. |
