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Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

ABSTRACT: Alloxan (AL)-generated Reactive Oxygen Species (ROS) selectively destroy insulin-producing pancreatic β-cells. A previous genome-wide scan (GWS) using a cohort of 296 F2 hybrids between NOD (AL-sensitive) and ALR (AL-resistant) mice identified linkages contributing to β-cell susceptibility or resistance to AL-induced diabetes on Chromosomes (Chr) 2, 3, 8, and a single nucleotide polymorphism in mt-Nd2 of the mitochondrial genome (mtDNA). AL treatment of congenic and consomic NOD mouse stocks confirmed resistance linked to both the mtDNA and the Chr 8 locus from ALR [NOD.mt^ALR.ALR-(D8Mit293-D8Mit137)]. To identify possible epistatic interactions, the GWS analysis was expanded to 678 F2 mice. ALR-derived diabetes-resistance linkages on Chr 8 as well as the mt-Nd2 ^a allele were confirmed and novel additional linkages on Chr 4, 5, 6, 7, and 13 were identified. Epistasis was observed between the linkages on Chr 8 and 2 and Chr 8 and 6. Furthermore, the mt-Nd2 genotype affected the epistatic interactions between Chr 8 and 2. These results demonstrate that a combination of nuclear-cytoplasmic genome interactions regulates β-cell sensitivity to ROS-mediated ALD.

SUBMITTER: Chen J

PROVIDER: S-EPMC9585181 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

Chen Jing J Li Renhua R Knapp Sarah S Zhu Guizhi G Whitener Robert L RL Leiter Edward H EH Mathews Clayton E CE

Frontiers in genetics 20221007

Alloxan (AL)-generated Reactive Oxygen Species (ROS) selectively destroy insulin-producing pancreatic β-cells. A previous genome-wide scan (GWS) using a cohort of 296 F2 hybrids between NOD (AL-sensitive) and ALR (AL-resistant) mice identified linkages contributing to β-cell susceptibility or resistance to AL-induced diabetes on Chromosomes (Chr) 2, 3, 8, and a single nucleotide polymorphism in <i>mt-Nd2</i> of the mitochondrial genome (mtDNA). AL treatment of congenic and consomic NOD mouse sto ...[more]

PMID: 36276935

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Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

Publications

Intergenomic and epistatic interactions control free radical mediated pancreatic β-cell damage.

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