PXD074604

PXD074604 is an original dataset announced via ProteomeXchange.

Title	Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity
Description	Missense variants in the O-GlcNAc transferase (OGT) gene have recently been shown to segregate with a syndromic form of intellectual disability (OGT-ID), underscoring the importance of protein O-GlcNAcylation in brain function. However, the underlying pathophysiological mechanisms linking ID to potential OGT malfunction—whether developmental, neurophysiological, or both—remain unclear. Here, we present comprehensive analyses encompassing behaviour and brain architecture of a rodent model carrying the pathogenic C921Y OGT-ID variant. These mice show a range of behavioural deficits, including hyperactivity, impulsivity, and associative learning phenotypes. Structural studies, using micro-computed tomography and magnetic resonance imaging, revealed reduced skull size, microcephaly, reduced cortical thickness and hypoplastic corpus callosum. Detailed histological analyses revealed dysplastic changes in the neocortex, predominantly affecting the superficial layers of cingulate cortex. Mechanistically, quantitative proteomic analyses revealed O-GlcNAc dyshomeostasis associated with distinct perturbed molecular pathways involved in brain development. Taken together, these data reveal neurodevelopmental defects associated with O-GlcNAc dyshomeostasis and provide a platform for dissecting mechanism and treatments of OGT-ID.
HostingRepository	PRIDE
AnnounceDate	2026-07-28
AnnouncementXML	Submission_2026-07-28_05:04:34.005.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD074604
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Carsten Scavenius
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: NEWT:10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2026-02-18 12:24:17	ID requested
1	2026-07-28 04:56:20	announced
⏵ 2	2026-07-28 05:04:34	announced	2026-07-28: Updated project metadata.

10.7554/ELIFE.107170.2;

submitter keyword: neurodevelopment,Intellectual disability, O-glycosylation, cortical dysplasia, behaviour, O-GlcNAc

Carsten Scavenius
contact affiliation	Molecular Biology and Genetics, Aarhus University
contact email	csss@mbg.au.dk
lab head
Carsten Scavenius
contact affiliation	Department og Molecular Biology and Genetics Aarhus University
contact email	csss@mbg.au.dk
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/2026/07/PXD074604

PRIDE project URI

• PRIDE
  1. PXD074604
     1. Label: PRIDE project
     2. Name: Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity