دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Neurodevelopmental defects in a mouse model of O-GlcNAc transferase intellectual disability.
المؤلفون: Authier F; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark., Ondruskova N; Department of Paediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, 128 08 Praha 2, Czech Republic., Ferenbach AT; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark., McNeilly AD; Division of Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK., van Aalten DMF; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus, Denmark.; Division of Cell and Developmental Biology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
المصدر: Disease models & mechanisms [Dis Model Mech] 2024 Apr 01; Vol. 17 (4). Date of Electronic Publication: 2024 Apr 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Company of Biologists Ltd Country of Publication: England NLM ID: 101483332 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1754-8411 (Electronic) Linking ISSN: 17548403 NLM ISO Abbreviation: Dis Model Mech Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge : Company of Biologists Ltd., c2008-
مواضيع طبية MeSH: N-Acetylglucosaminyltransferases*/metabolism , N-Acetylglucosaminyltransferases*/genetics , N-Acetylglucosaminyltransferases*/deficiency , Intellectual Disability*/genetics , Disease Models, Animal*, Animals ; Brain/pathology ; Brain/metabolism ; Phenotype ; Mice ; Neurodevelopmental Disorders/pathology ; Neurodevelopmental Disorders/genetics ; Neurodevelopmental Disorders/enzymology ; beta-N-Acetylhexosaminidases/metabolism ; Glycosylation ; Body Weight
مستخلص: 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.
Competing Interests: Competing interests The authors declare no competing or financial interests.
(© 2024. Published by The Company of Biologists Ltd.)
References: Neuron. 2002 Jul 18;35(2):243-54. (PMID: 12160743)
Dis Model Mech. 2023 Jun 1;16(6):. (PMID: 37334838)
J Biol Chem. 2017 Jul 28;292(30):12621-12631. (PMID: 28584052)
Nat Chem Biol. 2012 Jan 22;8(3):253-61. (PMID: 22267118)
Res Dev Disabil. 2011 Mar-Apr;32(2):419-36. (PMID: 21236634)
Cell Rep. 2021 Mar 30;34(13):108905. (PMID: 33789105)
Curr Biol. 2019 Oct 21;29(20):3359-3369.e4. (PMID: 31588002)
Proc Natl Acad Sci U S A. 2016 Dec 27;113(52):15120-15125. (PMID: 27956640)
Nat Genet. 2018 Jul;50(7):912-919. (PMID: 29942086)
J Am Chem Soc. 2003 Jun 4;125(22):6612-3. (PMID: 12769553)
Eur J Hum Genet. 2020 Jun;28(6):706-714. (PMID: 32080367)
Sci Rep. 2017 Apr 03;7:44921. (PMID: 28368052)
J Biol Chem. 2001 Mar 30;276(13):9838-45. (PMID: 11148210)
Mol Cell Proteomics. 2006 May;5(5):923-34. (PMID: 16452088)
J Biol Chem. 2021 Jan-Jun;296:100439. (PMID: 33610549)
Epilepsia. 2000 Jan;41(1):19-23. (PMID: 10643918)
Proc Natl Acad Sci U S A. 2019 Jul 23;116(30):14961-14970. (PMID: 31296563)
Hum Mol Genet. 2021 Dec 17;31(1):57-68. (PMID: 34346496)
J Neurosci. 2017 Feb 22;37(8):2125-2136. (PMID: 28115479)
Cell. 2012 Nov 9;151(4):709-723. (PMID: 23141534)
Brain Res. 2003 Mar 21;966(2):194-205. (PMID: 12618343)
Magn Reson Imaging. 2012 Nov;30(9):1323-41. (PMID: 22770690)
Genet Med. 2005 Nov-Dec;7(9):650-4. (PMID: 16301868)
Cell Signal. 2022 Feb;90:110201. (PMID: 34800629)
Nucleic Acids Res. 2020 Jun 4;48(10):5656-5669. (PMID: 32329777)
Annu Rev Nutr. 2013;33:205-29. (PMID: 23642195)
J Neurochem. 2003 Sep;86(5):1271-80. (PMID: 12911634)
Diabetologia. 2015 Dec;58(12):2867-76. (PMID: 26342595)
Cell. 2011 Feb 4;144(3):376-88. (PMID: 21295698)
J Neurosci. 2014 Jan 1;34(1):10-21. (PMID: 24381264)
Front Physiol. 2013 Mar 14;4:34. (PMID: 23504620)
Cell Chem Biol. 2018 May 17;25(5):513-518.e4. (PMID: 29606577)
Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13132-7. (PMID: 15340146)
J Neurochem. 2001 Dec;79(5):1080-9. (PMID: 11739622)
Nat Chem. 2022 Jul;14(7):831-840. (PMID: 35637289)
J Biol Chem. 2022 Sep;298(9):102276. (PMID: 35863433)
J Biol Chem. 2015 Mar 13;290(11):7097-113. (PMID: 25596529)
Mol Cell Biol. 2004 Feb;24(4):1680-90. (PMID: 14749383)
Proc Natl Acad Sci U S A. 2021 Jan 26;118(4):. (PMID: 33419956)
Zool Res. 2017 Jul 18;38(4):171-179. (PMID: 28825447)
J Biol Chem. 2008 Aug 1;283(31):21411-7. (PMID: 18519567)
J Biol Chem. 2017 Apr 14;292(15):6076-6085. (PMID: 28246173)
Methods. 2001 Dec;25(4):402-8. (PMID: 11846609)
Cell. 2014 Oct 9;159(2):306-17. (PMID: 25303527)
Biochem Biophys Res Commun. 2020 Nov 19;532(4):541-547. (PMID: 32896380)
J Biol Chem. 2018 Jul 6;293(27):10810-10824. (PMID: 29769320)
Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1684-1689. (PMID: 28143929)
Front Cell Dev Biol. 2022 Jan 17;9:784700. (PMID: 35111754)
Dev Neurobiol. 2009 Feb 1-15;69(2-3):162-73. (PMID: 19086029)
Annu Rev Biochem. 2011;80:825-58. (PMID: 21391816)
Neurosci Bull. 2022 Mar;38(3):263-274. (PMID: 34741260)
J Biol Chem. 1999 Nov 5;274(45):32015-22. (PMID: 10542233)
Med Res Arch. 2020 Jun;8(6):. (PMID: 34164576)
J Biol Chem. 2017 May 26;292(21):8948-8963. (PMID: 28302723)
Biochem J. 2021 Jul 30;478(14):2733-2758. (PMID: 34297044)
FEBS Lett. 2020 Feb;594(4):717-727. (PMID: 31627256)
Glycobiology. 2017 Oct 1;27(10):927-937. (PMID: 28922739)
Front Endocrinol (Lausanne). 2018 Oct 16;9:599. (PMID: 30464755)
Proc Natl Acad Sci U S A. 2000 May 23;97(11):5735-9. (PMID: 10801981)
معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; 110061 United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: O-GlcNAcylation; Intellectual disability; Vertebrate development
المشرفين على المادة: EC 2.4.1.- (N-Acetylglucosaminyltransferases)
EC 2.4.1.- (O-GlcNAc transferase)
EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
EC 3.2.1.50 (hexosaminidase C)
تواريخ الأحداث: Date Created: 20240403 Date Completed: 20240425 Latest Revision: 20240517
رمز التحديث: 20240517
مُعرف محوري في PubMed: PMC11095632
DOI: 10.1242/dmm.050671
PMID: 38566589
قاعدة البيانات: MEDLINE
الوصف
تدمد:1754-8411
DOI:10.1242/dmm.050671