Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit
Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the ge...
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The Company of Biologists
2018-04-01
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Series: | Disease Models & Mechanisms |
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Online Access: | http://dmm.biologists.org/content/11/4/dmm031542 |
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author | Mao Chen Bing Yao Qiangbing Yang Jichao Deng Yuning Song Tingting Sui Lina Zhou HaoBing Yao Yuanyuan Xu Hongsheng Ouyang Daxin Pang Zhanjun Li Liangxue Lai |
author_facet | Mao Chen Bing Yao Qiangbing Yang Jichao Deng Yuning Song Tingting Sui Lina Zhou HaoBing Yao Yuanyuan Xu Hongsheng Ouyang Daxin Pang Zhanjun Li Liangxue Lai |
author_sort | Mao Chen |
collection | DOAJ |
description | Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous (FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. |
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issn | 1754-8403 1754-8411 |
language | English |
last_indexed | 2024-12-12T14:40:25Z |
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publisher | The Company of Biologists |
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spelling | doaj.art-f503d2b367cb4b91a91f8416ce42aedd2022-12-22T00:21:16ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112018-04-0111410.1242/dmm.031542031542Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbitMao Chen0Bing Yao1Qiangbing Yang2Jichao Deng3Yuning Song4Tingting Sui5Lina Zhou6HaoBing Yao7Yuanyuan Xu8Hongsheng Ouyang9Daxin Pang10Zhanjun Li11Liangxue Lai12 Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Jilin Provincial Key Laboratory of Animal Embryo Engineering, Jilin University, Changchun 130062, China Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous (FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome.http://dmm.biologists.org/content/11/4/dmm031542Fibrillin-1CRISPR/Cas9Marfanoid-progeroid-lipodystrophy (MPL) syndromeRabbit |
spellingShingle | Mao Chen Bing Yao Qiangbing Yang Jichao Deng Yuning Song Tingting Sui Lina Zhou HaoBing Yao Yuanyuan Xu Hongsheng Ouyang Daxin Pang Zhanjun Li Liangxue Lai Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit Disease Models & Mechanisms Fibrillin-1 CRISPR/Cas9 Marfanoid-progeroid-lipodystrophy (MPL) syndrome Rabbit |
title | Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit |
title_full | Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit |
title_fullStr | Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit |
title_full_unstemmed | Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit |
title_short | Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit |
title_sort | truncated c terminus of fibrillin 1 induces marfanoid progeroid lipodystrophy mpl syndrome in rabbit |
topic | Fibrillin-1 CRISPR/Cas9 Marfanoid-progeroid-lipodystrophy (MPL) syndrome Rabbit |
url | http://dmm.biologists.org/content/11/4/dmm031542 |
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