O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward

Shao, Meiyue; Yang, Xiao; Zhang, Chen-Chun; Jiang, Chuanhai; Mao, Ying; Xu, Wendong; Ma, Lan; Wang, Feifei

doi:10.1007/s12264-021-00776-8

Cited by 7 publications

(2 citation statements)

References 45 publications

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“…Investigating the function of OGT in neurodevelopment and the brain has been hampered by mouse lethality caused by global loss of Ogt ( Shafi et al, 2000 ; O'Donnell et al, 2004 ). Although several brain-cell-specific Ogt knockout (KO) mouse models also lead to postnatal lethality, these have highlighted the role of OGT in neurodevelopment, neuronal survival and structure ( O'Donnell et al, 2004 ; Wheatley et al, 2019 ; Shao et al, 2022 ; Cheng et al, 2020 ; Wang et al, 2016 ). Modeling OGT-CDG in vivo will help to more precisely understand how OGT regulates processes that are essential for neurodevelopment and brain function.…”

Section: Introductionmentioning

confidence: 99%

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

Authier,

Ondruskova,

Ferenbach

et al. 2024

Disease Models &Amp; Mechanisms

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O-GlcNAcylation is a protein modification that is critical for vertebrate development, catalysed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). Missense mutations in OGT have recently been shown to segregate with a X-linked syndromic form of intellectual disability, OGT-linked Congenital Disorder of Glycosylation (OGT-CDG). Although OGT-CDG suggests a critical role of O-GlcNAcylation in 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 OGT/OGA levels 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 correlation in OGT-CDG in vivo and for the development of possible treatment avenues for this disorder.

show abstract

Section: Introductionmentioning

confidence: 99%

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

Authier,

Ondruskova,

Ferenbach

et al. 2024

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

show abstract

“…Investigating the function of OGT in neurodevelopment and the brain has been hampered by mouse lethality caused by global loss of Ogt (10,11). Although several brain cell specific Ogt knock out (KO) mouse models also lead to postnatal lethality, these have highlighted the role of OGT in neurodevelopment, neuronal survival and structure (11,28,(35)(36)(37). Modelling OGT-CDG in vivo will help to more precisely understand how OGT regulates processes that are essential for neurodevelopment and brain function.…”

Section: Introductionmentioning

confidence: 99%

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

Authier,

Ondruskova,

Ferenbach

et al. 2023

Preprint

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O-GlcNAcylation is a protein modification that is critical for vertebrate development, catalysed by O-GlcNAc transferase (OGT) and reversed by O-GlcNAcase (OGA). Missense mutations in OGT have recently been shown to segregate with a syndromic form of intellectual disability, OGT-linked Congenital Disorder of Glycosylation (OGT-CDG). Although OGT-CDG suggests a critical role of O-GlcNAcylation in neurodevelopment and/or cognitive function, the underlying pathophysiologic mechanisms remain unknown. Here we report three mouse lines that carry three different catalytically impaired OGT-CDG variants. These mice show altered O-GlcNAc homeostasis with decreased global O-GlcNAcylation and OGT/OGA levels in the brain. Phenotypic characterization of the mice revealed microcephaly and cognitive deficits including hyperactivity, anxiety and altered spatial working memory. These mouse models will serve as an important tool to study genotype-phenotype correlation in OGT-CDG in vivo and for the development of possible treatment avenues for this disorder.

show abstract

O-GlcNAcylation in Neuronal Development, Neurodegeneration, and Neurological Disorders

Yang,

Shu,

2024

Chemistry and Biology of O-GlcNAcylation

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O-GlcNAcylation in Ventral Tegmental Area Dopaminergic Neurons Regulates Motor Learning and the Response to Natural Reward

Cited by 7 publications

References 45 publications

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

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

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

O-GlcNAcylation in Neuronal Development, Neurodegeneration, and Neurological Disorders

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