Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE246162 | GEO | 2024/01/10

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (RNA)

Project description:Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of neurodegenerative diseases including 4H leukodystrophy. We developed a postnatal whole-body mouse model expressing pathogenic mutations in Polr3a to examine the molecular mechanisms by which reduced Pol III activity results primarily in central nervous system phenotypes. Polr3a mutant mice exhibit behavioral deficits, exocrine pancreatic atrophy and cerebral pathology. Transcriptome and immunohistochemistry analyses of cerebra show a reduction in most Pol III transcripts, induction of innate immune and integrated stress responses and cell type-specific gene expression changes reflecting neuron and oligodendrocyte loss and microglial activation. A global decrease in mature tRNA levels and an altered tRNA profile preceded cerebral neurodegeneration suggesting a causal role in disease initiation. In cerebella, heart and kidney, Pol III transcripts other than tRNAs were generally unaffected. The results suggest tissue-specific thresholds of sensitivity to defects in Pol III transcription.

2024-01-10 | GSE246160 | GEO

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (tRNA)

2024-01-10 | GSE246161 | GEO

Molecular basis of neurodegeneration in a mouse model of <i>Polr3</i>-related disease.

Project description:Pathogenic variants in subunits of RNA polymerase (Pol) III cause a spectrum of neurodegenerative diseases including 4H leukodystrophy. Disease onset occurs from infancy to early adulthood and is associated with a variable range and severity of neurological and non-neurological features. The molecular basis of disease pathogenesis is unknown. We developed a postnatal whole-body mouse model expressing pathogenic Polr3a mutations to examine the molecular mechanisms by which reduced Pol III transcription results primarily in central nervous system phenotypes. Polr3a mutant mice exhibit behavioral deficits, cerebral pathology and exocrine pancreatic atrophy. Transcriptome and immunohistochemistry analyses of cerebra during disease progression show a reduction in most Pol III transcripts, induction of innate immune and integrated stress responses and cell type-specific gene expression changes reflecting neuron and oligodendrocyte loss and microglial activation. Earlier in the disease when integrated stress and innate immune responses are minimally induced, mature tRNA sequencing revealed a global reduction in tRNA levels and an altered tRNA profile but no changes in other Pol III transcripts. Thus, changes in the size and/or composition of the tRNA pool have a causal role in disease initiation. Our findings reveal different tissue- and brain region-specific sensitivities to a defect in Pol III transcription.

| S-EPMC10760057 | biostudies-literature

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease

Project description:Molecular basis of neurodegeneration in a mouse model of Polr3-related disease

| PRJNA1031683 | ENA

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (RNA)

Project description:Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (RNA)

| PRJNA1031685 | ENA

Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (tRNA)

Project description:Molecular basis of neurodegeneration in a mouse model of Polr3-related disease (tRNA)

| PRJNA1031687 | ENA

Molecular characterization of colorectal cancer-related peritoneal metastatic disease

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-06-01 | GSE183917 | GEO

Molecular basis of Urostyle development

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-10-01 | GSE243236 | GEO

cGAS/STING drives ageing-related inflammation and neurodegeneration

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-08-20 | GSE234422 | GEO

Laser-microdissected tissue from Tg2576 and APPPS1 plaque-depositing mouse model of Alzheimer's disease

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-11-04 | E-GEOD-15128 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data