Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease

ABSTRACT: Dentatorubral-pallidoluysian atrophy (DRPLA) is a polyglutamine neurodegenerative disorder caused by CAG expansions in ATN1. To investigate its pathogenesis, we developed and characterized Drosophila models expressing human ATN1 with normal (Q7) or pathogenic (Q88) repeats.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE289036 | GEO | 2025/02/11

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

CAG repeat-binding small molecule improves repeat-length-dependent dysregulation of gene expression profiles in a mouse model of Dentatorubral–pallidoluysian atrophy

Project description:Dentatorubral–pallidoluysian atrophy (DRPLA) is a devastating genetic disease presenting myoclonus, epilepsy, ataxia, and dementia. DRPLA is caused by the expansion of a CAG repeat in the ATN1 gene. The expanded CAG repeats are unstable, and ongoing repeat expansions contribute to disease onset, progression and severity. Previously, we characterized a small molecule, naphthyridine–azaquinolone (NA), which binds to CAG slip-out structures and induces repeat contraction in Huntington’s disease mice. Here, we demonstrate that long-term intracerebroventricular infusion of NA leads to repeat contraction in a murine model of DRPLA. To identify the effects of NA on transcriptional regulation, we conducted comprehensive gene expression analysis using RNA sequencing (RNA-Seq) in striatum from PBS-treated and NA-treated DRPLA mice.

2022-09-08 | GSE183652 | GEO

Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease

Project description:Insights into dentatorubral-pallidoluysian atrophy from a new Drosophila model of disease

| PRJNA1220681 | ENA

PCR-free HiSeqX whole genome sequence data on 120 samples with triplet repeat expansions (premutation and full expansions)

Project description:Whole genome sequence (WGS) data was generated on 120 Coriell samples with the following validated repeat expansions: Fragile X Syndrome, Huntington disease, Friedreich’s ataxia, Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, Spinocerebellar Ataxia 1/3 and Dentatorubral-Pallidoluysian Atrophy. These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, PCR-free WGS data.

| EGAS00001002462 | EGA

Polyglutamine Atrophin provokes neurodegeneration in Drosophila

2011-03-01 | GSE26246 | GEO

Polyglutamine Atrophin provokes neurodegeneration in Drosophila

Project description:Dentatorubral-pallidoluysian Atrophy (DRPLA) is a human polyQ disease caused by the expansion of a CAG strech in the atrophin-1 (at-1) gene. In all vertebrates, a second atrophin gene (at-2) is present and it encodes a related protein void of polyQ tracks. In D.melanogaster there is one conserved Atrophin (Atro) gene, ubiquitously expressed, which contains all functional domains of vertebrate Atrophins, including two polyQ stretches. To understand to what extent transcriptional alterations cause neurodegeneration and are linked to the normal functions of Atrophin, we performed a genome wide transcriptional profiling in our Drosophila models, focusing on primary events that precede neurodegeneration. We have found that polyQ Atro downregulates fat, which protects from neurodegeneration and Atrophin toxicity trhough the Hippo kinase cascade. Neurodegeneration progression caused by poly glutamine expansions of the Atro gene is measured by mRNA expression profiles in 4 D.melanogaster genotypes: in wild-type animals (controls), animals constitutively expressing the wild-type Atro transgene, animals constitutively expressing the polyQ expanded Atro transgenes A66QC and A75QN. The expressions of the Atro genes are under a GMR-Gal4 driver repressed by a Gal80 universal repressor sensitive to temperature. When flies are raised at 18 C, the transgenes are not expressed, but their expression is switched on when they are shifted to the ageing protocol at 29 C at time point day 0. The neurodegeneration is assessed after 2 and 14 days post-high-temperature shift.

2011-03-01 | E-GEOD-26246 | biostudies-arrayexpress

Atrophin-1 Antisense Oligonucleotide Provides Robust Protection from Pathology in a Fully Humanized DRPLA Model

Project description:Dentatorubral-pallidoluysian atrophy (DRPLA) is a fatal neurodegenerative disease arising from a CAG repeat expansion in the atrophin-1 (ATN1) gene. Because DRPLA, like many repeat expansion disorders (REDs), arises predominantly from toxic gain-of-function mechanisms, we hypothesized that ATN1 knockdown would have therapeutic potential. To test this, we established the first fully-humanized mouse model of a RED, in which one allele of mouse Atn1 is completely replaced by human ATN1, including 112 pure CAG repeats. This novel approach to exploring RED biology provides significant advantages, notably the ability to test sequence-specific therapeutics targeting human sequences, even in introns and untranslated regions of pre-mRNA. We found that our model—the Atn1Q112/+ mouse—recapitulates key features of human DRPLA, including behavioral alterations, reduced brain size and aggregate accumulation. We treated Atn1Q112/+ mice with antisense oligonucleotides (ASOs) targeting mouse Atn1 (to probe for loss of function concerns), human ATN1, or a combination. Treatment with human, but not mouse, ATN1-targeting ASOs provides remarkable protection from a range of disease-related behavioral phenotypes, including aggregation of mutant ATN1 (mATN1), and marked rescue of transcriptional dysregulation in the cerebellum. These results have helped motivate an ongoing human clinical study of ASOs targeting ATN1 for DRPLA.

2025-05-05 | GSE296072 | GEO

CAG repeat-binding small molecule improves repeat-length-dependent dysregulation of gene expression profiles in a mouse model of Dentatorubral–pallidoluysian atrophy

Project description:CAG repeat-binding small molecule improves repeat-length-dependent dysregulation of gene expression profiles in a mouse model of Dentatorubral–pallidoluysian atrophy

| PRJNA761581 | ENA

Lack of RAN-mediated toxicity in Huntington’s disease knock-in mice

Project description:Identification of repeat-associated non-AUG (RAN) translation in trinucleotide (CAG) repeat diseases leads to an emerging concept that CAG repeat diseases are caused by non-polyglutamine products. Nonetheless, the exact contribution of RAN translation to the pathogenesis of CAG repeat diseases remains elusive. Via CRISPR/Cas9-mediated genome editing, we established new knock-in mouse models that harbor expanded CAG repeats in the mouse huntingtin gene, which express RAN translated products or polyglutamine products respectively. Here we report that RAN translation is not detected in the knock-in mouse models, and that only the expanded polyglutamine products can cause neuropathology and behavioral phenotypes. Therefore, polyglutamine products, rather than RAN translated products, play a major role in the pathogenesis of CAG repeat diseases.

2020-02-03 | GSE142603 | GEO

Transcriptomic profiling of spinal and bulbar muscular atrophy cultured embryonic motor neurons

Project description:Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease, is a slowly progressive adult-onset neuromuscular disease which results from a polyglutamine (polyQ) encoding CAG repeat expansion within the androgen receptor gene (AR). Despite the ubiquitous expression of the androgen receptor, it is unclear why motor neurons selectively degenerate and there are no effective treatments or disease modifying therapies for this debilitating disease. In order to identify potential therapeutic targets, we set out to establish the genes and molecular pathways involved in early motor neuron dysfunction in SBMA. We therefore undertook global transcriptomic profiling of cultured primary embryonic motor neurons from the spinal cord of AR100 mice, which model SBMA.. Four biological replicate samples were used for genome wide analysis using Affymetrix 430 v2.0 mouse arrays. Data was normalised using therobust multichip average (RMA) algorithm.

2019-05-02 | E-MTAB-6986 | biostudies-arrayexpress

Pseudouridine-dependent ribosome biogenesis selectively regulates translation of polyglutamine proteins during Drosophila oogenesis [pulldown]

Project description:Stem cells in many systems, including Drosophila germline stem cells (GSCs), have increased ribosome biogenesis and translation during terminal differentiation. Here, we show that pseudouridylation of ribosomal RNA (rRNA) mediated by the H/ACA box is required for ribosome biogenesis and oocyte specification. Reducing ribosome levels during differentiation decreased the translation of a subset of mRNAs that are enriched for CAG repeats and encodes polyglutamine-containing proteins, including differentiation factors such as RNA-binding Fox protein 1. Moreover, ribosomes were enriched at CAG repeats within transcripts during oogenesis. Increasing TOR activity to elevate ribosome levels in H/ACA box-depleted germlines suppressed the GSC differentiation defects, whereas germlines treated with the TOR inhibitor rapamycin had reduced levels of polyglutamine-containing proteins. Thus, ribosome biogenesis and ribosome levels can control stem cell differentiation via selective translation of CAG repeat-containing transcripts.

2023-11-22 | GSE206691 | GEO

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