| First Author | Chen J | Year | 2022 |
| Journal | Front Genet | Volume | 13 |
| Pages | 994501 | PubMed ID | 36276935 |
| Mgi Jnum | J:331073 | Mgi Id | MGI:7378955 |
| Doi | 10.3389/fgene.2022.994501 | Citation | Chen J, et al. (2022) Intergenomic and epistatic interactions control free radical mediated pancreatic beta-cell damage. Front Genet 13:994501 |
| abstractText | Alloxan (AL)-generated Reactive Oxygen Species (ROS) selectively destroy insulin-producing pancreatic beta-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 beta-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 beta-cell sensitivity to ROS-mediated ALD. |
