PXD047531

PXD047531 is an original dataset announced via ProteomeXchange.

Title	Gene-environment interaction elicits dystonia-like features and impaired translational regulation in a DYT-TOR1A mouse model
Description	DYT-TOR1A dystonia is a movement disorder characterized by involuntary muscle contractions. Despite being the most common monogenetic form of dystonia, its pathophysiolofy remains unclear. With a reduced penetrance of about 30%, there is a suggestion that extragenetic factors are needed to develeop a dystonic phenotype. In the present study, we induced a sciatic nerve crush injury in a genetically predisposed DYT-TOR1A mouse model (DYT1KI) to evoke a dystonic phenotype. Subsequently, we employed a multi-omic approach to uncover novel pathophysiological pathways associated with DYT-TOR1A dystonia. Utilizing a deep-learning-based characterization of the dystonic phenotype, we observed that nerve-injured DYT1KI animals exhibited significantly more dystonia-like movement (DLM) compared to naive DYT1KI animals, with noticeable effects as early as two weeks post-surgery. Moreover, nerve-injured DT1KI mice displayed significantly more DLM than their wildtype (wt) counterparts starting 6 weeks post-injury. In the cerebellum of nerve-injured wt mice, multi-omice analysis indicated regulatory changes in translation-related processes, a phenomenon not observed in the cerebellum of nerve-injured DYT1KI mice; instead, these changes were localized to the cortex and striatum. Our findings suggest a failure of translational compensatory mechanisms in the cerebellum of phenotypic DY1KI mice displaying DLM, while dysregulations in translation in the cortex and striatum likely contribute to the promotion of the dystonic phenotype.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_06:32:10.226.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Colette Reinhold
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-05 04:07:47	ID requested
1	2024-03-05 07:16:22	announced
⏵ 2	2024-10-22 06:32:11	announced	2024-10-22: Updated project metadata.

10.1016/j.nbd.2024.106453;

Reinhold C, Knorr S, McFleder RL, Rauschenberger L, Muthuraman M, Arampatzi P, Gr, ä, fenhan T, Schlosser A, Sendtner M, Volkmann J, Ip CW, Gene-environment interaction elicits dystonia-like features and impaired translational regulation in a DYT-TOR1A mouse model. Neurobiol Dis, 193():106453(2024) [pubmed]

submitter keyword: second-hit hypothesis, multi-omic,DYT-TOR1A

Prof. Dr. Chi Wang Ip
contact affiliation	Neurologische Klinik und Poliklinik des Universitätsklinikums Neurology Josef-Schneider-Straße 11 97080 Würzburg Germany
contact email	ip_C@ukw.de
lab head
Colette Reinhold
contact affiliation	University Hospital Wuerzburg
contact email	colette.reinhold@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/03/PXD047531

PRIDE project URI

• PRIDE
  1. PXD047531
     1. Label: PRIDE project
     2. Name: Gene-environment interaction elicits dystonia-like features and impaired translational regulation in a DYT-TOR1A mouse model