Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease

Abstract Danon disease (DD) is caused by the absence or malfunction of lysosomal-associated membrane protein 2 (LAMP2). Although Lamp2-deficient mice and DD patients have similar characteristics, these mice have clear limitations and are clinically inconsistent. The aim of our paper is to outline th...

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Autores principales:	Shuoyi Ma, Miao Zhang, Shuai Zhang, Jing Wang, Xia Zhou, Guanya Guo, Lu Wang, Min Wang, Zhengwu Peng, Changcun Guo, Xiaohong Zheng, Xinmin Zhou, Jingbo Wang, Ying Han
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42546d8a5af4421d9c104a2c696c869a
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spelling	oai:doaj.org-article:42546d8a5af4421d9c104a2c696c869a2021-12-02T12:32:09ZCharacterisation of Lamp2-deficient rats for potential new animal model of Danon disease10.1038/s41598-018-24351-w2045-2322https://doaj.org/article/42546d8a5af4421d9c104a2c696c869a2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24351-whttps://doaj.org/toc/2045-2322Abstract Danon disease (DD) is caused by the absence or malfunction of lysosomal-associated membrane protein 2 (LAMP2). Although Lamp2-deficient mice and DD patients have similar characteristics, these mice have clear limitations and are clinically inconsistent. The aim of our paper is to outline the characteristics of Lamp2-deficient rats and to contrast this model with currently available DD mouse models. The baseline levels of some serum enzymes were elevated in Lamp2 y/− rats along with hypercholesterolemia and hyperglycaemia at 8 weeks. Echocardiography showed that IVSd (1.500 ± 0.071 vs. 2.200 ± 1.147, P < 0.01) and LVPWd (1.575 ± 0.063 vs. 1.850 ± 0.029, P < 0.01) were significantly increased, and GCS (−13.20 ± 0.4814 vs. −6.954 ± 0.665) and GRS (21.42 ± 1.807 vs. 7.788 ± 1.140) were sharply decreased. Meanwhile, substantial myocyte disruption, hypertrophic muscle fibres, interstitial fibrosis and microvascular hyperplasia could be observed in the heart tissue. Lamp2y/− rats also displayed abnormal behaviours in the open field and fear conditioning tests. Notably, Lamp2y/− rats manifested other system dysfunctions, such as retinopathy, chronic kidney injury and sterility. Based on these results, Lamp2-deficient rats exhibited greater similarity to DD patients in terms of onset and multisystem lesions than did mouse models, and these rats could be used as a valuable animal model for DD.Shuoyi MaMiao ZhangShuai ZhangJing WangXia ZhouGuanya GuoLu WangMin WangZhengwu PengChangcun GuoXiaohong ZhengXinmin ZhouJingbo WangYing HanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shuoyi Ma Miao Zhang Shuai Zhang Jing Wang Xia Zhou Guanya Guo Lu Wang Min Wang Zhengwu Peng Changcun Guo Xiaohong Zheng Xinmin Zhou Jingbo Wang Ying Han Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
description	Abstract Danon disease (DD) is caused by the absence or malfunction of lysosomal-associated membrane protein 2 (LAMP2). Although Lamp2-deficient mice and DD patients have similar characteristics, these mice have clear limitations and are clinically inconsistent. The aim of our paper is to outline the characteristics of Lamp2-deficient rats and to contrast this model with currently available DD mouse models. The baseline levels of some serum enzymes were elevated in Lamp2 y/− rats along with hypercholesterolemia and hyperglycaemia at 8 weeks. Echocardiography showed that IVSd (1.500 ± 0.071 vs. 2.200 ± 1.147, P < 0.01) and LVPWd (1.575 ± 0.063 vs. 1.850 ± 0.029, P < 0.01) were significantly increased, and GCS (−13.20 ± 0.4814 vs. −6.954 ± 0.665) and GRS (21.42 ± 1.807 vs. 7.788 ± 1.140) were sharply decreased. Meanwhile, substantial myocyte disruption, hypertrophic muscle fibres, interstitial fibrosis and microvascular hyperplasia could be observed in the heart tissue. Lamp2y/− rats also displayed abnormal behaviours in the open field and fear conditioning tests. Notably, Lamp2y/− rats manifested other system dysfunctions, such as retinopathy, chronic kidney injury and sterility. Based on these results, Lamp2-deficient rats exhibited greater similarity to DD patients in terms of onset and multisystem lesions than did mouse models, and these rats could be used as a valuable animal model for DD.
format	article
author	Shuoyi Ma Miao Zhang Shuai Zhang Jing Wang Xia Zhou Guanya Guo Lu Wang Min Wang Zhengwu Peng Changcun Guo Xiaohong Zheng Xinmin Zhou Jingbo Wang Ying Han
author_facet	Shuoyi Ma Miao Zhang Shuai Zhang Jing Wang Xia Zhou Guanya Guo Lu Wang Min Wang Zhengwu Peng Changcun Guo Xiaohong Zheng Xinmin Zhou Jingbo Wang Ying Han
author_sort	Shuoyi Ma
title	Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
title_short	Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
title_full	Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
title_fullStr	Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
title_full_unstemmed	Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease
title_sort	characterisation of lamp2-deficient rats for potential new animal model of danon disease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/42546d8a5af4421d9c104a2c696c869a
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Characterisation of Lamp2-deficient rats for potential new animal model of Danon disease

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