Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA383702 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Here we analyse transcriptome profiles from laser captured lower motor neurons between wild type, heterozygous and homozygous TDP-43 Q331K knockin mice
2018-03-08 | GSE99352 | GEO
Project description:Here we analyse transcriptome profiles within the frontal cortex between wild type, heterozygous and homozygous TDP-43 Q331K knockin mice at 20 months of age (C57BL/6)
2018-04-01 | GSE112575 | GEO
Project description:Frontal cortex transcriptomic analysis of a TDP-43 Q331K knock-in mouse [5month]
| PRJNA388188 | ENA
Project description:Lower motor neuron transcriptomic analysis of a TDP-43 Q331K knock-in mouse
| PRJNA388189 | ENA
Project description:Here we analyse transcriptome profiles within the frontal cortex between wild type, heterozygous and homozygous TDP-43 Q331K knock-in mice
2018-03-08 | GSE99353 | GEO
Project description:A key pathological feature of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) is the loss of nuclear localization and the accumulation of cytoplasmic inclusions of hyperphosphorylated TAR-DNA binding protein 43 (TDP-43). TDP-43 is a nucleic acid-binding protein involved in transcriptional repression, mRNA splicing, and the regulation of retrotransposable elements (RTEs) and endogenous retroviruses (ERVs). RTEs and ERVs are mobile genetic elements that constitute about 45% of our genome. These virus-like elements encode the capacity to replicate through an RNA intermediate and insert cDNA copies at de novo chromosomal locations. Their expression is a proven source of DNA damage and inflammatory signaling. Research in Drosophila has demonstrated a causal role of RTEs/ERVs in mediating both intracellular toxicity of TDP-43 and the intercellular spread of these toxic effects from glia to neurons. RTEs and ERVs are inappropriately expressed in postmortem tissues from ALS, FTD, and Alzheimer’s Disease (AD) patients, as well as in cell culture in response to TDP-43 disruption, suggesting that the findings in Drosophila may be conserved across species. But the role of RTEs and ERVs has not yet been examined in a vertebrate model of TDP-43 pathology. To investigate the functional contributions of RTEs in vertebrates, we utilized an established transgenic mouse model that overexpresses moderate levels of either human wild-type TDP-43 (hTDP-43-WT) or a mutant version with a specific causal amino acid substitution (hTDP-43-Q331K) associated with some inherited forms of the disease. Through RNA-sequencing of the motor cortex, and imaging of a LINE-1-EGFP retrotransposon indicator cassette, we found that the TDP-43 transgenic animals exhibit broad expression of RTEs and ERVs, along with replication of LINE-1 in glia and neurons in the motor cortex. This expression begins at the age of onset of neurological phenotypes, earlier in the hTDP-43-Q331K animals and much later in hTDP-43-WT. Although the motor defects progressively worsen over time, the LINE-1-EGFP replication reporter transiently labels spatially clustered groups of neurons and glia at the time of onset of motor symptoms. These EGFP-labeled neurons undergo cell death and are therefore lost over time. Unlabeled cells also die as a function of distance from the clusters of LINE-1-EGFP labeled neurons and glial cells. Together, these findings support the hypothesis that TDP-43 pathology triggers RTE/ERV expression in the motor cortex, that such expression marks cells for programmed cell death, with non-cell autonomous effects on nearby neurons and glial cells.
2025-06-23 | GSE300423 | GEO
Project description:Lipidomic analysis was performed to identify the lipid alteration in the liver of TDP-43 Q331K Tmem106b knockout mice
2025-01-21 | MSV000096905 | MassIVE
Project description:Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features, including accumulation of the RNA binding protein TDP-43. TDP-43 regulates RNA homeostasis, but it remains unclear whether RNA stability is affected in these disorders. We use Bru-seq and BruChase-seq to assess genome-wide RNA stability in ALS patient-derived cells, demonstrating profound destabilization of ribosomal and mitochondrial transcripts. This pattern is recapitulated by TDP-43 overexpression, suggesting a primary role for TDP-43 in RNA destabilization, and in post-mortem samples from ALS and FTD patients. Proteomics and functional studies illustrate corresponding reductions in mitochondrial components and compensatory increases in protein synthesis. Collectively, these observations suggest that TDP-43 deposition leads to targeted RNA instability in ALS and FTD, and may ultimately cause cell death by disrupting energy production and protein synthesis pathways.
2018-07-24 | PXD009969 | Pride
Project description:The aim of this study is to understand the mechanisms of TDP-43 neurotoxicity. Here, we perform a RNA-Seq analysis in TDP-43 gain-of-fucntion (GOF) , TDP-43 loss-of-function and wild-type late pupae heads (73-90 hours APF) and perform TDP-43 GOF vs wild type and TDP-43 LOF vs wild-type differential expression analysis to show that both mechanisms presents defects in ecdysone receptor (ECR)-dependeint transcriptional program switching, and strongly deregulate expression from the neuronal microtubule associated protien Map205. RNA-seq was performed in two wild-type D.melanogaster biological replicates (Canton S, w1118 ), four biological replicates for TDP-43 (LOF) with two distinct genotypes (dTDP-43Δ142/Df(2R)106,dTDP-43Δ23/Δ142 ) and two TDP-43 GOF biological replicates (act5c>dTDP-43 ).
2013-01-22 | E-GEOD-42844 | biostudies-arrayexpress