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Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models
Posttranslational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, >150 human GPI-anchored proteins have been discovered and ~30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161520/ https://www.ncbi.nlm.nih.gov/pubmed/33607654 http://dx.doi.org/10.1093/hmg/ddab052 |
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author | Kandasamy, Lenin C Tsukamoto, Mina Banov, Vitaliy Tsetsegee, Sambuu Nagasawa, Yutaro Kato, Mitsuhiro Matsumoto, Naomichi Takeda, Junji Itohara, Shigeyoshi Ogawa, Sonoko Young, Larry J Zhang, Qi |
author_facet | Kandasamy, Lenin C Tsukamoto, Mina Banov, Vitaliy Tsetsegee, Sambuu Nagasawa, Yutaro Kato, Mitsuhiro Matsumoto, Naomichi Takeda, Junji Itohara, Shigeyoshi Ogawa, Sonoko Young, Larry J Zhang, Qi |
author_sort | Kandasamy, Lenin C |
collection | PubMed |
description | Posttranslational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, >150 human GPI-anchored proteins have been discovered and ~30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) catalyzes the very first step of GPI anchor biosynthesis. Patients carrying a mutation of the PIGA gene usually suffer from inherited glycosylphosphatidylinositol deficiency (IGD) with intractable epilepsy and intellectual developmental disorder. We generated three mouse models with PIGA deficits specifically in telencephalon excitatory neurons (Ex-M-cko), inhibitory neurons (In-M-cko) or thalamic neurons (Th-H-cko), respectively. Both Ex-M-cko and In-M-cko mice showed impaired long-term fear memory and were more susceptible to kainic acid-induced seizures. In addition, In-M-cko demonstrated a severe limb-clasping phenotype. Hippocampal synapse changes were observed in Ex-M-cko mice. Our Piga conditional knockout mouse models provide powerful tools to understand the cell-type specific mechanisms underlying inherited GPI deficiency and to test different therapeutic modalities. |
format | Online Article Text |
id | pubmed-8161520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81615202021-06-02 Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models Kandasamy, Lenin C Tsukamoto, Mina Banov, Vitaliy Tsetsegee, Sambuu Nagasawa, Yutaro Kato, Mitsuhiro Matsumoto, Naomichi Takeda, Junji Itohara, Shigeyoshi Ogawa, Sonoko Young, Larry J Zhang, Qi Hum Mol Genet General Article Posttranslational modification of a protein with glycosylphosphatidylinositol (GPI) is a conserved mechanism exists in all eukaryotes. Thus far, >150 human GPI-anchored proteins have been discovered and ~30 enzymes have been reported to be involved in the biosynthesis and maturation of mammalian GPI. Phosphatidylinositol glycan biosynthesis class A protein (PIGA) catalyzes the very first step of GPI anchor biosynthesis. Patients carrying a mutation of the PIGA gene usually suffer from inherited glycosylphosphatidylinositol deficiency (IGD) with intractable epilepsy and intellectual developmental disorder. We generated three mouse models with PIGA deficits specifically in telencephalon excitatory neurons (Ex-M-cko), inhibitory neurons (In-M-cko) or thalamic neurons (Th-H-cko), respectively. Both Ex-M-cko and In-M-cko mice showed impaired long-term fear memory and were more susceptible to kainic acid-induced seizures. In addition, In-M-cko demonstrated a severe limb-clasping phenotype. Hippocampal synapse changes were observed in Ex-M-cko mice. Our Piga conditional knockout mouse models provide powerful tools to understand the cell-type specific mechanisms underlying inherited GPI deficiency and to test different therapeutic modalities. Oxford University Press 2021-02-19 /pmc/articles/PMC8161520/ /pubmed/33607654 http://dx.doi.org/10.1093/hmg/ddab052 Text en © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | General Article Kandasamy, Lenin C Tsukamoto, Mina Banov, Vitaliy Tsetsegee, Sambuu Nagasawa, Yutaro Kato, Mitsuhiro Matsumoto, Naomichi Takeda, Junji Itohara, Shigeyoshi Ogawa, Sonoko Young, Larry J Zhang, Qi Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title | Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title_full | Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title_fullStr | Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title_full_unstemmed | Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title_short | Limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
title_sort | limb-clasping, cognitive deficit and increased vulnerability to kainic acid-induced seizures in neuronal glycosylphosphatidylinositol deficiency mouse models |
topic | General Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161520/ https://www.ncbi.nlm.nih.gov/pubmed/33607654 http://dx.doi.org/10.1093/hmg/ddab052 |
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