Journal article
Deficiency in mitochondrial complex i Activity Due to Ndufs6 gene trap insertion induces renal disease
JM Forbes, BX Ke, TV Nguyen, DC Henstridge, SA Penfold, A Laskowski, KC Sourris, LN Groschner, ME Cooper, DR Thorburn, MT Coughlan
Antioxidants and Redox Signaling | MARY ANN LIEBERT, INC | Published : 2013
Abstract
Aims: Defects in the activity of enzyme complexes of the mitochondrial respiratory chain are thought to be responsible for several disorders, including renal impairment. Gene mutations that result in complex I deficiency are the most common oxidative phosphorylation disorders in humans. To determine whether an abnormality in mitochondrial complex I per se is associated with development of renal disease, mice with a knockdown of the complex I gene, Ndufs6 were studied. Results: Ndufs6 mice had a partial renal cortical complex I deficiency; Ndufs6gt/gt, 32% activity and Ndufs6gt/+, 83% activity compared with wild-type mice. Both Ndufs6gt/+ and Ndufs6 gt/gt mice exhibited hallmarks of renal dis..
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Funding Acknowledgements
The authors would like to thank Amy Morley, Vicki Thallas-Bonke, Brooke Harcourt, Edward Grixti, and Maryann Arnstein for their technical expertise. This work was completed with support from the Juvenile Diabetes Research Foundation (JDRF), the National Health and Medical Research Council of Australia (NHMRC), and the Victorian Government's Operational Infrastructure Support Program. Melinda Coughlan holds a Skip Martin Australian Diabetes Society Early Career Fellowship. Josephine Forbes is an NHMRC Research Fellow. Darren Henstridge is supported by a Postdoctoral Fellowship from The National Heart Foundation of Australia. David Thorburn is an NHMRC Principal Research Fellow. Mark Cooper is an NHMRC Australia Fellow as well as a JDRF scholar.