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(searched for: Mitochondrial Reactive Oxygen Species and Nephrolithiasis)
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Sciprofile linkCaroline M. Gorvin, Bushra N. Ahmad, Michael J. Stechman, Nellie Y. Loh, Tertius A. Hough, Paul Leo, Mhairi Marshall, Siddharth Sethi, Liz Bentley, Sian Piret, et al.
Published: 14 December 2018
by Wiley
Journal of Bone and Mineral Research, Volume 34, pp 497-507; doi:10.1002/jbmr.3624

Abstract: Renal calcification (RCALC) resulting in
nephrolithiasis
and nephrocalcinosis, which affects ∼10% of adults by 70 years of age, involves environmental and genetic etiologies. Thus,
nephrolithiasis
and nephrocalcinosis occurs as an inherited disorder in ∼65% of patients, and may be associated with endocrine and metabolic disorders including: primary hyperparathyroidism, hypercalciuria, renal tubular acidosis, cystinuria, and hyperoxaluria. Investigations of families with
nephrolithiasis
and nephrocalcinosis have identified some causative genes, but further progress is limited as large families are unavailable for genetic studies. We therefore embarked on establishing mouse models for hereditary
nephrolithiasis
and nephrocalcinosis by performing abdominal X‐rays to identify renal opacities in N‐ethyl‐N‐nitrosourea (ENU)‐mutagenized mice. This identified a mouse with RCALC inherited as an autosomal dominant trait, designated RCALC type 2 (RCALC2). Genomewide mapping located the Rcalc2 locus to a ∼16‐Mbp region on chromosome 11D‐E2 and whole‐exome sequence analysis identified a heterozygous mutation in the DNA polymerase gamma‐2, accessory subunit (Polg2) resulting in a nonsense mutation, Tyr265Stop (Y265X), which co‐segregated with RCALC2. Kidneys of mutant mice (Polg2+ / Y265X) had lower POLG2 mRNA and protein expression, compared to wild‐type littermates (Polg2+/+). The Polg2+/Y265X and Polg2+ / + mice had similar plasma concentrations of sodium, potassium, calcium, phosphate, chloride, urea, creatinine, glucose, and alkaline phosphatase activity; and similar urinary fractional excretion of calcium, phosphate, oxalate, and protein. Polg2 encodes the minor subunit of the
mitochondrial
DNA (mtDNA) polymerase and the mtDNA content in Polg2+ / Y265X kidneys was reduced compared to Polg2+/+ mice, and cDNA expression profiling revealed differential expression of 26 genes involved in several biological processes including
mitochondrial
DNA function, apoptosis, and ubiquitination, the complement pathway, and inflammatory pathways. In addition, plasma of Polg2+ / Y265X mice, compared to Polg2+ / + littermates had higher levels of
reactive
oxygen
species
. Thus, our studies have identified a mutant mouse model for inherited renal calcification associated with a Polg2 nonsense mutation. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Sciprofile linkTakahiro Yasui, Atsushi Okada, Shuzo Hamamoto, Ryosuke Ando, Sciprofile linkKazumi Taguchi, Keiichi Tozawa, Kenjiro Kohri
Published: 18 August 2016
by Wiley
International Journal of Urology, Volume 24, pp 32-38; doi:10.1111/iju.13187

The publisher has not yet granted permission to display this abstract.
Minu Sharma, Tanzeer Kaur, Sciprofile linkS. K. Singla
Published: 1 March 2016
Mitochondrion, Volume 27, pp 15-24; doi:10.1016/j.mito.2016.01.002

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Sciprofile linkCaigan Du, Sciprofile linkXimo Wang, Huifang Chen
Systems Biology of Free Radicals and Antioxidants pp 2605-2624; doi:10.1007/978-3-642-30018-9_187

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T Allard, T Wenner, H J Greten, T Efferth
Published: 1 January 2013
Current Medicinal Chemistry, Volume 20

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Cheng Yang Li, Yao Liang Deng, Bing Hua Sun
Urological Research, Volume 37, pp 211-220; doi:10.1007/s00240-009-0197-1

The publisher has not yet granted permission to display this abstract.
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