Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy

Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD c...

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Autores principales: Kuwayama, Ryoko, Suzuki, Keiichiro, Nakamura, Jun, Aizawa, Emi, Yoshioka, Yoshichika, Ikawa, Masahito, Nabatame, Shin, Inoue, Ken-ichi, Shimmyo, Yoshiari, Ozono, Keiichi, Kinoshita, Taroh, Murakami, Yoshiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166810/
https://www.ncbi.nlm.nih.gov/pubmed/35661110
http://dx.doi.org/10.1038/s41467-022-30847-x
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author Kuwayama, Ryoko
Suzuki, Keiichiro
Nakamura, Jun
Aizawa, Emi
Yoshioka, Yoshichika
Ikawa, Masahito
Nabatame, Shin
Inoue, Ken-ichi
Shimmyo, Yoshiari
Ozono, Keiichi
Kinoshita, Taroh
Murakami, Yoshiko
author_facet Kuwayama, Ryoko
Suzuki, Keiichiro
Nakamura, Jun
Aizawa, Emi
Yoshioka, Yoshichika
Ikawa, Masahito
Nabatame, Shin
Inoue, Ken-ichi
Shimmyo, Yoshiari
Ozono, Keiichi
Kinoshita, Taroh
Murakami, Yoshiko
author_sort Kuwayama, Ryoko
collection PubMed
description Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs.
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spelling pubmed-91668102022-06-05 Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy Kuwayama, Ryoko Suzuki, Keiichiro Nakamura, Jun Aizawa, Emi Yoshioka, Yoshichika Ikawa, Masahito Nabatame, Shin Inoue, Ken-ichi Shimmyo, Yoshiari Ozono, Keiichi Kinoshita, Taroh Murakami, Yoshiko Nat Commun Article Inherited glycosylphosphatidylinositol (GPI) deficiency (IGD) is caused by mutations in GPI biosynthesis genes. The mechanisms of its systemic, especially neurological, symptoms are not clarified and fundamental therapy has not been established. Here, we report establishment of mouse models of IGD caused by PIGO mutations as well as development of effective gene therapy. As the clinical manifestations of IGD are systemic and lifelong lasting, we treated the mice with adeno-associated virus for homology-independent knock-in as well as extra-chromosomal expression of Pigo cDNA. Significant amelioration of neuronal phenotypes and growth defect was achieved, opening a new avenue for curing IGDs. Nature Publishing Group UK 2022-06-03 /pmc/articles/PMC9166810/ /pubmed/35661110 http://dx.doi.org/10.1038/s41467-022-30847-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kuwayama, Ryoko
Suzuki, Keiichiro
Nakamura, Jun
Aizawa, Emi
Yoshioka, Yoshichika
Ikawa, Masahito
Nabatame, Shin
Inoue, Ken-ichi
Shimmyo, Yoshiari
Ozono, Keiichi
Kinoshita, Taroh
Murakami, Yoshiko
Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title_full Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title_fullStr Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title_full_unstemmed Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title_short Establishment of mouse model of inherited PIGO deficiency and therapeutic potential of AAV-based gene therapy
title_sort establishment of mouse model of inherited pigo deficiency and therapeutic potential of aav-based gene therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166810/
https://www.ncbi.nlm.nih.gov/pubmed/35661110
http://dx.doi.org/10.1038/s41467-022-30847-x
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