Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability

Florence Authier, Nina Ondruskova, Andrew T. Ferenbach, Alison D. McNeilly, Daan M.F. van Aalten

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Abstract

The addition of O-linked β-N-acetylglucosamine (O-GlcNAc) to proteins (referred to as O-GlcNAcylation) is a modification that is crucial for vertebrate development. O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). Missense variants of OGT have recently been shown to segregate with an X-linked syndromic form of intellectual disability, OGT-linked congenital disorder of glycosylation (OGT-CDG). Although the existence of OGT-CDG suggests that O-GlcNAcylation is crucial for neurodevelopment and/or cognitive function, the underlying pathophysiologic mechanisms remain unknown. Here we report a mouse line that carries a catalytically impaired OGT-CDG variant. These mice show altered O-GlcNAc homeostasis with decreased global O-GlcNAcylation and reduced levels of OGT and OGA in the brain. Phenotypic characterization of the mice revealed lower body weight associated with reduced body fat mass, short stature and microcephaly. This mouse model will serve as an important tool to study genotype-phenotype correlations in OGT-CDG in vivo and for the development of possible treatment avenues for this disorder.

OriginalsprogEngelsk
TidsskriftDisease Models & Mechanisms
Vol/bind17
Nummer4
ISSN1754-8403
DOI
StatusUdgivet - 1 apr. 2024

Fingeraftryk

Dyk ned i forskningsemnerne om 'Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability'. Sammen danner de et unikt fingeraftryk.

Citationsformater