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A systems approach identifies progeroid Ercc1[-/Δ] mice as a model system for kidney aging.

ABSTRACT: Using these samples, it has been shown that the transcriptional landscape in glomeruli of Ercc1[-/Δ] mice at a rather young age of 14 weeks mimics that of mice which have undergone real-life renal aging. Thus, young Ercc1[-/Δ] mice can be used as a model system for glomerular aging in future studies.

ORGANISM(S): Mus musculus

PROVIDER: GSE43061 | GEO | 2012/12/21

SECONDARY ACCESSION(S): PRJNA184201

REPOSITORIES: GEO

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A systems approach identifies progeroid Ercc1[-/Δ] mice as a model system for kidney aging.

Project description:Using these samples, it has been shown that the transcriptional landscape in glomeruli of Ercc1[-/Δ] mice at a rather young age of 14 weeks mimics that of mice which have undergone real-life renal aging. Thus, young Ercc1[-/Δ] mice can be used as a model system for glomerular aging in future studies. The RNAs origin from glomerular tissues of mice of 2 distinct genotypes at 3 distinct stages of age. Between 3 and 6 replicates have been prepared per group.

2012-12-21 | E-GEOD-43061 | biostudies-arrayexpress

Transcription profiling of liver from wild type or Ercc1 mutant mice

Project description:The XPF-ERCC1 endonuclease is required for repair of helix-distorting DNA damage and interstrand crosslinks. Here we have engineered a severe mutation in Ercc1 gene (in which the last 7 amino acids are missing; named as "Ercc1-delta") leading to extreme sensitivity to DNA crosslinks and progeria.To investigate whether a disturbance in growth and metabolism could explain the pronounced accelerated organismal deterioration seen in Ercc1 delta mice, we evaluated the liver transcriptome of 16-week-old wt and mutant mice (n=6). At this age, the Ercc1-delta mice have not yet become cachectic.

2008-06-01 | E-MEXP-1503 | biostudies-arrayexpress

Unprecedented life- and healthspan extension and genome preservation by diet restriction in DNA repair deficient progeroid Ercc1∆/- mice [RNA-seq]

Project description:In this study, we investigate the anti-aging response induced by dietary restriction (DR) on gene expression level. For this, we carried out Ribosomal RNA depleted Total RNA sequencing in 16 weeks old Ercc1∆/- ad libidum (AL), DR and wt mice.

2016-09-09 | GSE77494 | GEO

Supplementation with Lactobacillus plantarum WCFS1 prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1-/Δ7 Mice

Project description:Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-wk bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1-/Δ7 mice, which have a median lifespan of ~20wk, and their wild-type littermates. The colonic barrier in Ercc1-/Δ7 mice was characterized by a thin (<10µm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1-/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1-/Δ7 mice. L. plantarum- and L. casei-treated Ercc1-/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1-/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly.

2016-10-19 | GSE87368 | GEO

Transcription profiling of liver from Ercc1-/- mice and wild type littermates to investigate features of premature aging

Project description:To investigate the cause of the premature aging features in the Ercc1-/- mouse, we compared the entire transcriptome of the Ercc1-/- mouse liver to that of wildtype littermates at the age of 15 days, when the Ercc1-/- mice reached their maximal weight and had symptoms of progeria, yet overall pathology was still limited. The liver was selected because the tissue showed several well-defined histological changes associated with aging (polyploidy and intranuclear inclusions) as well as evidence that it is responding to endogenous genotoxic stress (stabilized p53).

2006-12-21 | E-MEXP-834 | biostudies-arrayexpress

Down-regulation of cholesterol biosynthesis in forebrains of ERCC1-deficient mice

Project description:Background: Several genetic defects of the nucleotide excision repair (NER) pathway, including deficiency of the Excision Repair Cross-Complementing rodent repair deficiency, complementation group 1 (ERCC1), result in pre-mature aging, impaired growth, microcephaly and delayed development of the cerebellum. Such a phenotype also occurs in ERCC1-knockout mice which survive for up to 4 weeks after birth. Therefore, we analyzed cerebellar and hippocamapal transcriptomes of these animals at 3 weeks of age to identify the candidate mechanisms underlying brain consequences of reduced ERCC1 activity. Results: In the cerebellum, the most prominent change was upregulation of genes that are associated with gliosis. Although Purkinje cell degeneration has been reported in some mouse strains with NER impairment, Purkinje cell transcriptome was mostly unaffected by the ERCC1 knockout. In the hippocampus, the gliosis response was minimal. Instead, there was an extensive downregulation of genes related to lipid metabolism including several enzymes of the cholesterol biosynthesis pathway as well as lipoproteins and plasma membrane proteins. Reduced expression of the cholesterol biosynthesis pathway genes was also present in the neocortex of adult mice whose ERCC1 gene was replaced by a mutant allele with a partial activity. Conclusions: Downregulation of forebrain cholesterol biosynthesis genes is a newly identified consequence of ERCC1 deficiency. Its presence in adult mice suggests that it is not a secondary consequence of brain growth impairment. Instead, reduced cholesterol biosynthesis may contribute to such an impairment as well as affect function of mature synapses.

2011-08-16 | GSE31199 | GEO

Unprecedented life- and healthspan extension and genome preservation by diet restriction in DNA repair deficient progeroid Ercc1 Δ/- mice

Project description:Unprecedented life- and healthspan extension and genome preservation by diet restriction in DNA repair deficient progeroid Ercc1 Δ/- mice

| PRJNA310633 | ENA

Down-regulation of cholesterol biosynthesis in forebrains of ERCC1-deficient mice

2011-08-15 | E-GEOD-31199 | biostudies-arrayexpress

Transcriptome profiling of NER progeroid animals treated with an NF-kB inhibitor.

Project description:NBD treatment of animals: Sibling pairs of Ercc1-/delta mice housed in a single cage were treated with 8K-NBD or 8K-mNBD 10 mg/kg three times per week intraperitoneally by an investigator blinded as to the treatment group. Treatment began at 5 weeks of age before the animals were symptomatic and continued throughout their lifespan. Mice were euthanized via CO2 inhalation at 12 or 18-20 weeks of age and tissues isolated. 8K-NBD (KKKKKKKKGGTALDWSWLQTE) and inactive 8K-mutant NBD (8K-mNBD) (KKKKKKKKGGTALDASALQTE) were synthesized at the University of Pittsburgh Peptide facility. Peptides were dissolved in DMSO at 40uM and stored at -80 C until dilution in PBS directly before use.

2012-07-01 | E-MEXP-3615 | biostudies-arrayexpress

Gene expression profiling of Ercc1-/- and age-matched wt pancreata

Project description:Total RNA was isolated from wt and Ercc1-/- pancreata from 15 days old C57BL/6J wt and Ercc1-/- mice

2021-05-15 | E-MTAB-10393 | biostudies-arrayexpress