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Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice

The asparaginase and isoaspartyl peptidase 1 (ASRGL1) is an L-asparaginase and beta-aspartyl peptidase enzyme that may be involved in the formation of L-aspartate, a neurotransmitter that can operate as an excitatory neurotransmitter in some brain regions. Although variants in ASRGL1 have been repor...

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Autores principales: Zhou, Yu, Tian, Wanli, Jiang, Xiaoyan, Yang, Huining, Jiang, Zhilin, Li, Xiao, Jiang, Dan, Sun, Kuanxiang, Yang, Yeming, Liu, Wenjing, Zhu, Xianjun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805730/
https://www.ncbi.nlm.nih.gov/pubmed/35118070
http://dx.doi.org/10.3389/fcell.2021.783547
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author Zhou, Yu
Tian, Wanli
Jiang, Xiaoyan
Yang, Huining
Jiang, Zhilin
Li, Xiao
Jiang, Dan
Sun, Kuanxiang
Yang, Yeming
Liu, Wenjing
Zhu, Xianjun
author_facet Zhou, Yu
Tian, Wanli
Jiang, Xiaoyan
Yang, Huining
Jiang, Zhilin
Li, Xiao
Jiang, Dan
Sun, Kuanxiang
Yang, Yeming
Liu, Wenjing
Zhu, Xianjun
author_sort Zhou, Yu
collection PubMed
description The asparaginase and isoaspartyl peptidase 1 (ASRGL1) is an L-asparaginase and beta-aspartyl peptidase enzyme that may be involved in the formation of L-aspartate, a neurotransmitter that can operate as an excitatory neurotransmitter in some brain regions. Although variants in ASRGL1 have been reported in retinitis pigmentosa (RP) patients, the in vivo functions and mechanisms of ASRGL in RP remains unknown due to the lack of suitable disease models. To explore the role of ASRGL in RP, we generated an Asrgl1 knockout mouse model (Asrgl1 KO) using the CRISPR/Cas9 technique. Asrgl1 ablation in mice led to an attenuated electroretinogram (ERG) response around 8 months. The thickness of the outer nuclei layer (ONL) started to decrease around 9 months in Asrgl1 KO mice and gradually intensified at 12 and 15 months. Immunostaining revealed thinner inner segment (IS) and thinner outer segment (OS) as well as the progressive degeneration of rod and cone cells in Asrgl1 KO mice. One hundred forty-nine transcriptional differentially expressed genes (DEGs) were found by RNA-seq in Asrgl1 KO retina. These DEGs were linked to a number of biological processes that were considerably enriched, including gastrointestinal disease and organismal injury and abnormalities. By analysis of canonical pathways, glucocorticoid receptor signaling was the most significant canonical pathway altered in Asrgl1 KO retina. Several molecules, including NFE2L2, IL-4, Foxp3, and Fos, were in the central nodes of the interaction network in Asrgl1 KO retina. In summary, our study provided a knockout mouse model for a better understanding of the molecular mechanism for ASRGL1-related RP.
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spelling pubmed-88057302022-02-02 Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice Zhou, Yu Tian, Wanli Jiang, Xiaoyan Yang, Huining Jiang, Zhilin Li, Xiao Jiang, Dan Sun, Kuanxiang Yang, Yeming Liu, Wenjing Zhu, Xianjun Front Cell Dev Biol Cell and Developmental Biology The asparaginase and isoaspartyl peptidase 1 (ASRGL1) is an L-asparaginase and beta-aspartyl peptidase enzyme that may be involved in the formation of L-aspartate, a neurotransmitter that can operate as an excitatory neurotransmitter in some brain regions. Although variants in ASRGL1 have been reported in retinitis pigmentosa (RP) patients, the in vivo functions and mechanisms of ASRGL in RP remains unknown due to the lack of suitable disease models. To explore the role of ASRGL in RP, we generated an Asrgl1 knockout mouse model (Asrgl1 KO) using the CRISPR/Cas9 technique. Asrgl1 ablation in mice led to an attenuated electroretinogram (ERG) response around 8 months. The thickness of the outer nuclei layer (ONL) started to decrease around 9 months in Asrgl1 KO mice and gradually intensified at 12 and 15 months. Immunostaining revealed thinner inner segment (IS) and thinner outer segment (OS) as well as the progressive degeneration of rod and cone cells in Asrgl1 KO mice. One hundred forty-nine transcriptional differentially expressed genes (DEGs) were found by RNA-seq in Asrgl1 KO retina. These DEGs were linked to a number of biological processes that were considerably enriched, including gastrointestinal disease and organismal injury and abnormalities. By analysis of canonical pathways, glucocorticoid receptor signaling was the most significant canonical pathway altered in Asrgl1 KO retina. Several molecules, including NFE2L2, IL-4, Foxp3, and Fos, were in the central nodes of the interaction network in Asrgl1 KO retina. In summary, our study provided a knockout mouse model for a better understanding of the molecular mechanism for ASRGL1-related RP. Frontiers Media S.A. 2022-01-18 /pmc/articles/PMC8805730/ /pubmed/35118070 http://dx.doi.org/10.3389/fcell.2021.783547 Text en Copyright © 2022 Zhou, Tian, Jiang, Yang, Jiang, Li, Jiang, Sun, Yang, Liu and Zhu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Zhou, Yu
Tian, Wanli
Jiang, Xiaoyan
Yang, Huining
Jiang, Zhilin
Li, Xiao
Jiang, Dan
Sun, Kuanxiang
Yang, Yeming
Liu, Wenjing
Zhu, Xianjun
Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title_full Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title_fullStr Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title_full_unstemmed Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title_short Deletion of Asrgl1 Leads to Photoreceptor Degeneration in Mice
title_sort deletion of asrgl1 leads to photoreceptor degeneration in mice
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8805730/
https://www.ncbi.nlm.nih.gov/pubmed/35118070
http://dx.doi.org/10.3389/fcell.2021.783547
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