Ontology highlight
ABSTRACT:
PROVIDER: PRJNA374339 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5244970_1.fastq.gz | Fastqsanger.gz | |||
| SRR5244970_2.fastq.gz | Fastqsanger.gz | |||
| SRR5244980_1.fastq.gz | Fastqsanger.gz | |||
| SRR5244980_2.fastq.gz | Fastqsanger.gz | |||
| SRR5244990_1.fastq.gz | Fastqsanger.gz |
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Project description:Studying whether removal of base-excision repair from mitochondria will result into increase in mitochondrial DNA (mtDNA) mutation load. The endogenous genes of OGG1 and MUTYH DNA glycosylases were modified to lack the genomic region encoding for the predicted mitochondrial targeting sequence. The mouse lines used: A mouse line that lacks the region encoding for the mitochondrial targeting sequence (L2 to W23) of OGG1 (Ogg1 dMTS mice). A mouse line that lacks the region encoding the mitochondrial targeting sequence (K2 to P33) of MUTYH (Mutyh dMTS mice). To accumulate mutations to the mitochondrial DNA these mice were bred double homozygous Mutyh dMTS x Ogg1 dMTS mice as a maternal lineage for five consecutive generations and mitochondrial DNA from liver was extracted from the offspring and sequenced with Illumina. OGG1 and MUTYH are involved in repair of 8-oxo-dG from DNA. 8-oxo-dG can be a mutagenic lesion because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6532 | biostudies-arrayexpress
Project description:Mitochondrial complex I, the largest enzyme complex of the mitochondrial oxidative phosphorylation machinery, has been proposed to contribute to variety of age-related pathological alterations as well as longevity. The enzyme complex-consisting proteins are encoded by both nuclear- (nDNA) and mitochondrial DNA (mtDNA). While some association studies of mtDNA-encoded complex I genes and lifespan in humans have been reported, experimental evidence and functional consequence of such variants are limited to studies using invertebrate models. Here, we present experimental evidence that a homoplasmic mutation in mitochondrially encoded complex I gene, mt-Nd2, modulates lifespan by altering cellular tryptophan levels and consequently ageing-related pathways in mice. A conplastic mouse strain carrying a mutation at m.4738C>A in mt-Nd2 lived significantly shorter than the controls. The same mutation led to higher susceptibility to glucose intolerance induced by high fat diet feeding. These phenotypes were not observed in mice carrying a mutation in another mtDNA-encoded complex I gene, mt-Nd5, suggesting functional relevance of particular mutations in complex I to ageing and age-related diseases.
2019-12-23 | GSE114256 | GEO
Project description:Accumulating evidences suggest a link between mitochondrial dysfunction and female reproduction decline. To directly and systematically figure out the influence of mitochondrial DNA (mtDNA) mutation on oocyte quality and embryo development, we used an mtDNA mutator mouse model (D257A) that harbors a proofreading-deficient version of PolgA. Here we showed that D257A mice developed a profound reduction of fertility at 19-week of age, and accumulated twofold more increase in the levels of point mutations in oocyte mtDNA. Following ovarian hyper-stimulation, we found oocyte numbers retrieved from WT and D257A mice were comparable until 19 weeks of age, while with a half reduced number of oocyte ovulated in D257A mice thereafter. We further found the oocyte quality based on mitochondrial distribution, meiotic spindle assembly, chromosomal segregation and ATP content at 19 weeks of age was identical in both group. Meanwhile, the ovulated oocytes can initiate and sustain early embryo development after in vitro fertilization, and reach the blastocyst stage with no obvious defects compared to WTs. Of note, post-implantation developmental defects were observed in D257A embryos, as revealed by fetal growth retardation and decreased ratios of pups delivered. Furthermore, genome-wide methylation analysis revealed global hypomethylation across the genome of D257A oocytes, with a dramatic reduce in genome repetitive-elements, like DNA transposon, LINEs and SINEs regions. In conclusion, our study presents the direct experimental investigation of the effect of mtDNA mutation on oocyte and embryo competence, and demonstrates altered DNA methylation in oocyte may represent a critical mechanism that mediates the phenotypic defects of mtDNA mutation in post-implantation development.
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Project description:Genes expressed in age-induced mitochondrial DNA deletion mutation containing / Electron Transport abnormal cells
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Project description:To study whether increase in mitochondrial oxidative stress (SOD2 removal) and decrease in mitochondrial DNA repair (Ogg1 dMTS) results into increase in mitochondrial DNA mutation load. Oxidative stress has been suggested to induce mutations in mtDNA. To verify this, we extracted and sequenced (Illumina) mitochondrial DNA from heart Sod2 knockout animals that were also deficient for mitochondrial base-excision repair. The repair deficiency was induced by removing the genomic region encoding for the predicted mitochondrial targeting sequence from endogenous OGG1 (L2 to W23) called Ogg1 dMTS mice, thus excluding the protein from mitochondria. OGG1 is a DNA glycosylase that recognizes and repairs 8-oxo-dG damage from DNA. Oxidative stress can induce 8-oxo-dG lesions, thus we removed the mitochondrial matrix localized superoxide dismutase (SOD2) from these mice to increase the level of oxidative stress. 8-oxo-dG lesion can be mutagenic because some DNA repair polymerases are known to erroneously incorporate adenosine opposite to 8-oxo-dG during replication leading to GC>TA transversion mutations.
2018-07-13 | E-MTAB-6533 | biostudies-arrayexpress
Project description:Background: Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are also implicated in ageing processes. Results: Primary fibroblasts of the conplastic mouse strain C57BL/6J-mtALR/LTJ with a mutation at position nt4738 resulting in a single nucleotide exchange (leucine to methionine) in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain show higher enzyme activity and ATP production and lower ROS production than control fibroblasts. Furthermore, Nd2-mutant fibroblasts show a higher proliferation rate and a reduction of senescence markers. Transcriptome analysis reveals members of the p38MAPK pathway as being significantly downregulated in Nd2-mutant mice as compared with controls. In line with this, inhibition of p38MAPK with SB203580 enhanced the proliferation and reduced cytokine secretion in senescent Nd2-mutant fibroblasts. Conclusion: Taken together, we report Nd2 as a new mitochondrial gene with age-protective function in mice, and possibly in humans, which interferes with age-related signaling pathways. MouseRef-8 v2.0 Expression BeadChips of 8 samples of skin fibroblasts; 4 samples of fibroblasts from 4 mice of C57BL/6J-mtALR/LtJ (Nd2-mutant) and 4 samples of fibroblasts from 4 mice of C57BL/6J-mtAKR/J (control)
2014-11-22 | E-GEOD-63551 | biostudies-arrayexpress
Project description:Background: Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are also implicated in ageing processes. Results: Primary fibroblasts of the conplastic mouse strain C57BL/6J-mtALR/LTJ with a mutation at position nt4738 resulting in a single nucleotide exchange (leucine to methionine) in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain show higher enzyme activity and ATP production and lower ROS production than control fibroblasts. Furthermore, Nd2-mutant fibroblasts show a higher proliferation rate and a reduction of senescence markers. Transcriptome analysis reveals members of the p38MAPK pathway as being significantly downregulated in Nd2-mutant mice as compared with controls. In line with this, inhibition of p38MAPK with SB203580 enhanced the proliferation and reduced cytokine secretion in senescent Nd2-mutant fibroblasts. Conclusion: Taken together, we report Nd2 as a new mitochondrial gene with age-protective function in mice, and possibly in humans, which interferes with age-related signaling pathways.
2014-11-22 | GSE63551 | GEO
Project description:Recently, we have identified a point mutation V338Y in mammalian nuclear-encoded mitochondrial protein MrpS5 that confers error-prone mitochondrial protein synthesis. In-vivo, mutation V338Y was associated with a distinct phenotype including impaired mitochondrial function, enhanced susceptibility to noise-induced hearing damage, anxiety-related behavioral alterations, and age-associated metabolic changes in muscle. To challenge the link between V338Y-mediated misreading and in-vivo phenotype, we introduced mutation G315R into the MRPS5 gene; MRPS5 G315R is homologous to the established bacterial ram mutation uS5 G104R. In contrast to the phylogenetically closely related bacterial translation, the corresponding MRPS5 G315R mutation did not affect the accuracy of mitochondrial protein synthesis. In addition, in the absence of mitochondrial misreading, homozygous mutant MRPS5G315R/G315R mice did not show phenotype distinct from wild-type animals.
2022-04-27 | GSE195772 | GEO
Project description:Camk2-mutPolg mouse carries the transgene of mutated polymerase gamma under Camk2 promoter. By the mutation, polymerase gamma lost its proof-reading activity, and thus tg mouse accumulates deletions and mutations in mitochondrial DNA in neurons. This mouse showed behavioral alterations similar to mood disorders. To examine the epigenetic status in the brain cells, we have performed promoter-wide DNA methylation analysis in neurons and nonneurons of the tg mouse.
2022-01-12 | GSE171120 | GEO