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A novel and efficient murine model of Bietti crystalline dystrophy
Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease, resulting in blindness in most patients. The etiology and development mechanism of it remain unclear. Given the defects in previous mouse models of BCD, we generated a new Cyp4v3(−/−) mouse model, using CRISPR/Ca...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906172/ https://www.ncbi.nlm.nih.gov/pubmed/35230417 http://dx.doi.org/10.1242/dmm.049222 |
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author | Wang, Yafang Liu, Yang Liu, Shu Li, Xiaomeng Liu, Xinxin Jiao, Ming Yang, Yuqin Luo, Xueting Wang, Fenghua Wan, Xiaoling Sun, Xiaodong |
author_facet | Wang, Yafang Liu, Yang Liu, Shu Li, Xiaomeng Liu, Xinxin Jiao, Ming Yang, Yuqin Luo, Xueting Wang, Fenghua Wan, Xiaoling Sun, Xiaodong |
author_sort | Wang, Yafang |
collection | PubMed |
description | Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease, resulting in blindness in most patients. The etiology and development mechanism of it remain unclear. Given the defects in previous mouse models of BCD, we generated a new Cyp4v3(−/−) mouse model, using CRISPR/Cas9 technology, for investigating the pathogenesis of BCD. We estimated the ocular phenotypes by fundus imaging, optical coherence tomography (OCT) and full-field scotopic electroretinography, and investigated the histological features by Hematoxylin and Eosin staining, Oil Red O staining and immunofluorescence. This model effectively exhibited age-related progression that mimicked the human ocular phenotypes. Moreover, gas chromatography-mass spectrometry and RNA-seq analysis indicated that the defect of Cyp4v3 led to the abnormal lipid metabolism, inflammation activation and oxidative stress of retina. Notably, inflammation activation and oxidative stress could also promote the progression of BCD in light-induced retinal degeneration. In conclusion, our data provided evidence that we established a novel and more effective Cyp4v3 knockout preclinical mouse model for BCD, which served as a useful tool for evaluating the effect of drugs and gene therapy in vivo. |
format | Online Article Text |
id | pubmed-8906172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-89061722022-03-09 A novel and efficient murine model of Bietti crystalline dystrophy Wang, Yafang Liu, Yang Liu, Shu Li, Xiaomeng Liu, Xinxin Jiao, Ming Yang, Yuqin Luo, Xueting Wang, Fenghua Wan, Xiaoling Sun, Xiaodong Dis Model Mech Research Article Bietti crystalline dystrophy (BCD) is an autosomal recessive inherited retinal disease, resulting in blindness in most patients. The etiology and development mechanism of it remain unclear. Given the defects in previous mouse models of BCD, we generated a new Cyp4v3(−/−) mouse model, using CRISPR/Cas9 technology, for investigating the pathogenesis of BCD. We estimated the ocular phenotypes by fundus imaging, optical coherence tomography (OCT) and full-field scotopic electroretinography, and investigated the histological features by Hematoxylin and Eosin staining, Oil Red O staining and immunofluorescence. This model effectively exhibited age-related progression that mimicked the human ocular phenotypes. Moreover, gas chromatography-mass spectrometry and RNA-seq analysis indicated that the defect of Cyp4v3 led to the abnormal lipid metabolism, inflammation activation and oxidative stress of retina. Notably, inflammation activation and oxidative stress could also promote the progression of BCD in light-induced retinal degeneration. In conclusion, our data provided evidence that we established a novel and more effective Cyp4v3 knockout preclinical mouse model for BCD, which served as a useful tool for evaluating the effect of drugs and gene therapy in vivo. The Company of Biologists Ltd 2022-03-01 /pmc/articles/PMC8906172/ /pubmed/35230417 http://dx.doi.org/10.1242/dmm.049222 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Wang, Yafang Liu, Yang Liu, Shu Li, Xiaomeng Liu, Xinxin Jiao, Ming Yang, Yuqin Luo, Xueting Wang, Fenghua Wan, Xiaoling Sun, Xiaodong A novel and efficient murine model of Bietti crystalline dystrophy |
title | A novel and efficient murine model of Bietti crystalline dystrophy |
title_full | A novel and efficient murine model of Bietti crystalline dystrophy |
title_fullStr | A novel and efficient murine model of Bietti crystalline dystrophy |
title_full_unstemmed | A novel and efficient murine model of Bietti crystalline dystrophy |
title_short | A novel and efficient murine model of Bietti crystalline dystrophy |
title_sort | novel and efficient murine model of bietti crystalline dystrophy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906172/ https://www.ncbi.nlm.nih.gov/pubmed/35230417 http://dx.doi.org/10.1242/dmm.049222 |
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