Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation
X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have th...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Molecular Neuroscience |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00453/full |
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Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ding Chen Ding Chen Tao Xu Tao Xu Mengjun Tu Mengjun Tu Jinlin Xu Jinlin Xu Chenchen Zhou Chenchen Zhou Lulu Cheng Lulu Cheng Ruqing Yang Tanchu Yang Weiwei Zheng Weiwei Zheng Xiubin He Xiubin He Ruzhi Deng Ruzhi Deng Xianglian Ge Xianglian Ge Jin Li Jin Li Zongming Song Zongming Song Zongming Song Junzhao Zhao Feng Gu Feng Gu |
| spellingShingle |
Ding Chen Ding Chen Tao Xu Tao Xu Mengjun Tu Mengjun Tu Jinlin Xu Jinlin Xu Chenchen Zhou Chenchen Zhou Lulu Cheng Lulu Cheng Ruqing Yang Tanchu Yang Weiwei Zheng Weiwei Zheng Xiubin He Xiubin He Ruzhi Deng Ruzhi Deng Xianglian Ge Xianglian Ge Jin Li Jin Li Zongming Song Zongming Song Zongming Song Junzhao Zhao Feng Gu Feng Gu Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation Frontiers in Molecular Neuroscience retina X-linked juvenile retinoschisis knock-in mice disease model genome editing technologies |
| author_facet |
Ding Chen Ding Chen Tao Xu Tao Xu Mengjun Tu Mengjun Tu Jinlin Xu Jinlin Xu Chenchen Zhou Chenchen Zhou Lulu Cheng Lulu Cheng Ruqing Yang Tanchu Yang Weiwei Zheng Weiwei Zheng Xiubin He Xiubin He Ruzhi Deng Ruzhi Deng Xianglian Ge Xianglian Ge Jin Li Jin Li Zongming Song Zongming Song Zongming Song Junzhao Zhao Feng Gu Feng Gu |
| author_sort |
Ding Chen |
| title |
Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation |
| title_short |
Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation |
| title_full |
Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation |
| title_fullStr |
Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation |
| title_full_unstemmed |
Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel Mutation |
| title_sort |
recapitulating x-linked juvenile retinoschisis in mouse model by knock-in patient-specific novel mutation |
| publisher |
Frontiers Media S.A. |
| series |
Frontiers in Molecular Neuroscience |
| issn |
1662-5099 |
| publishDate |
2018-01-01 |
| description |
X-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction. |
| topic |
retina X-linked juvenile retinoschisis knock-in mice disease model genome editing technologies |
| url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00453/full |
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doaj-a524905c67804ac7bbcf941f0806b82c2020-11-24T22:20:48ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-01-011010.3389/fnmol.2017.00453318282Recapitulating X-Linked Juvenile Retinoschisis in Mouse Model by Knock-In Patient-Specific Novel MutationDing Chen0Ding Chen1Tao Xu2Tao Xu3Mengjun Tu4Mengjun Tu5Jinlin Xu6Jinlin Xu7Chenchen Zhou8Chenchen Zhou9Lulu Cheng10Lulu Cheng11Ruqing Yang12Tanchu Yang13Weiwei Zheng14Weiwei Zheng15Xiubin He16Xiubin He17Ruzhi Deng18Ruzhi Deng19Xianglian Ge20Xianglian Ge21Jin Li22Jin Li23Zongming Song24Zongming Song25Zongming Song26Junzhao Zhao27Feng Gu28Feng Gu29State Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaDepartment of Ophthalmology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou, ChinaThe Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaState Key Laboratory of Ophthalmology, Optometry and Vision Science, School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical University, Wenzhou, ChinaMinistry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology and Optometry, Wenzhou, ChinaX-linked juvenile retinoschisis (XLRS) is a retinal disease caused by mutations in the gene encoding retinoschisin (RS1), which leads to a significant proportion of visual impairment and blindness. To develop personalized genome editing based gene therapy, knock-in animal disease models that have the exact mutation identified in the patients is extremely crucial, and that the way which genome editing in knock-in animals could be easily transferred to the patients. Here we recruited a family diagnosed with XLRS and identified the causative mutation (RS1, p.Y65X), then a knock-in mouse model harboring this disease-causative mutation was generated via TALEN (transcription activator-like effector nucleases). We found that the b-wave amplitude of the ERG of the RS1-KI mice was significantly decreased. Moreover, we observed that the structure of retina in RS1-KI mice has become disordered, including the disarray of inner nuclear layer and outer nuclear layer, chaos of outer plexiform layer, decreased inner segments of photoreceptor and the loss of outer segments. The novel knock-in mice (RS1-KI) harboring patient-specific mutation will be valuable for development of treatment via genome editing mediated gene correction.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00453/fullretinaX-linked juvenile retinoschisisknock-inmicedisease modelgenome editing technologies |