Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 1)

ABSTRACT: We isolated RNA from cerebella dissected from En1-Cre; Cicflox/flox and Cicflox/+ littermates at one year of age

ORGANISM(S): Mus musculus

PROVIDER: GSE108254 | GEO | 2018/04/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 2)

Project description:We isolated RNA from cerebella dissected from Pcp2-ATXN1[82Q], Pcp2-ATXN1[82Q]V591A;S602D, and wild-type littermates at one year of age

2018-04-24 | GSE108255 | GEO

ATXN1-CIC Complex Is the Primary Driver of Cerebellar Pathology in Spinocerebellar Ataxia Type 1 through a Gain-of-Function Mechanism.

Project description:Polyglutamine (polyQ) diseases are caused by expansion of translated CAG repeats in distinct genes leading to altered protein function. In spinocerebellar ataxia type 1 (SCA1), a gain of function of polyQ-expanded ataxin-1 (ATXN1) contributes to cerebellar pathology. The extent to which cerebellar toxicity depends on its cognate partner capicua (CIC), versus other interactors, remains unclear. It is also not established whether loss of the ATXN1-CIC complex in the cerebellum contributes to disease pathogenesis. In this study, we exclusively disrupt the ATXN1-CIC interaction in vivo and show that it is at the crux of cerebellar toxicity in SCA1. Importantly, loss of CIC in the cerebellum does not cause ataxia or Purkinje cell degeneration. Expression profiling of these gain- and loss-of-function models, coupled with data from iPSC-derived neurons from SCA1 patients, supports a mechanism in which gain of function of the ATXN1-CIC complex is the major driver of toxicity.

| S-EPMC6422678 | biostudies-literature

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1

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

2018-04-24 | GSE108256 | GEO

Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1.

Project description:Spinocerebellar ataxia type 1 (SCA1) is a paradigmatic neurodegenerative disease in that it is caused by a mutation in a broadly expressed protein, ATXN1; however, only select populations of cells degenerate. The interaction of polyglutamine-expanded ATXN1 with the transcriptional repressor CIC drives cerebellar Purkinje cell pathogenesis; however, the importance of this interaction in other vulnerable cells remains unknown. Here, we mutated the 154Q knockin allele of Atxn1154Q/2Q mice to prevent the ATXN1-CIC interaction globally. This normalized genome-wide CIC binding; however, it only partially corrected transcriptional and behavioral phenotypes, suggesting the involvement of additional factors in disease pathogenesis. Using unbiased proteomics, we identified three ATXN1-interacting transcription factors: RFX1, ZBTB5, and ZKSCAN1. We observed altered expression of RFX1 and ZKSCAN1 target genes in SCA1 mice and patient-derived iNeurons, highlighting their potential contributions to disease. Together, these data underscore the complexity of mechanisms driving cellular vulnerability in SCA1.

| S-EPMC9957872 | biostudies-literature

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 2)

Project description:Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 2)

| PRJNA422988 | ENA

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 1)

Project description:Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1 (part 1)

| PRJNA422989 | ENA

Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1

Project description:Gain of function of the ATXN1-CIC complex drives cerebellar pathology in Spinocerebellar ataxia type 1

| PRJNA422984 | ENA

Disruption of the ATXN1-CIC complex reveals the role of additional nuclear ATXN1 interactors in spinocerebellar ataxia type 1

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

2022-12-13 | GSE218302 | GEO

In Vivo Molecular Signatures of Cerebellar Pathology in Spinocerebellar Ataxia Type 3.

Project description:BackgroundNo treatment exists for the most common dominantly inherited ataxia Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3). Successful evaluation of candidate therapeutics will be facilitated by validated noninvasive biomarkers of disease pathology recapitulated by animal models.ObjectiveWe sought to identify shared in vivo neurochemical signatures in two mouse models of SCA3 that reflect the human disease pathology.MethodsCerebellar neurochemical concentrations in homozygous YACMJD84.2 (Q84/Q84) and hemizygous CMVMJD135 (Q135) mice were measured by in vivo magnetic resonance spectroscopy at 9.4 tesla. To validate the neurochemical biomarkers, levels of neurofilament medium (NFL; indicator of neuroaxonal integrity) and myelin basic protein (MBP; indicator of myelination) were measured in cerebellar lysates from a subset of mice and patients with SCA3. Finally, NFL and MBP levels were measured in the cerebellar extracts of Q84/Q84 mice upon silencing of the mutant ATXN3 gene.ResultsBoth Q84/Q84 and Q135 mice displayed lower N-acetylaspartate than wild-type littermates, indicating neuroaxonal loss/dysfunction, and lower myo-inositol and total choline, indicating disturbances in phospholipid membrane metabolism and demyelination. Cerebellar NFL and MBP levels were accordingly lower in both models as well as in the cerebellar cortex of patients with SCA3 than controls. Importantly, N-acetylaspartate and total choline correlated with NFL and MPB, respectively, in Q135 mice. Long-term sustained RNA interference (RNAi)-mediated reduction of ATXN3 levels increased NFL and MBP in Q84/Q84 cerebella.ConclusionsN-acetylaspartate, myo-inositol, and total choline levels in the cerebellum are candidate biomarkers of neuroaxonal and oligodendrocyte pathology in SCA3, aspects of pathology that are reversible by RNAi therapy. © 2020 International Parkinson and Movement Disorder Society.

| S-EPMC7572607 | biostudies-literature

Ronin expression induces ataxia and cerebellar degeneration in a mouse model of ataxia

Project description:Gene expression studies in cerebella isolated from 5 week old wildtype or transgenic mice (C57BL/6) overexpressing Ronin in Purkinje cells were generated. RNA was isolated from cerebella of 3 transgenic animals at 5 weeks of agee and 3 wildtype litter mates.

2021-06-10 | GSE176518 | 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