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

被引：12

作者：

Ma, Shuoyi ^{[1
,2
]}

Zhang, Miao ^{[1
,2
]}

Zhang, Shuai ^{[1
,2
]}

Wang, Jing ^{[3
]}

Zhou, Xia ^{[1
,2
]}

Guo, Guanya ^{[1
,2
]}

Wang, Lu ^{[1
,2
]}

Wang, Min ^{[1
,2
]}

Peng, Zhengwu ^{[4
]}

Guo, Changcun ^{[1
,2
]}

Zheng, Xiaohong ^{[1
,2
]}

Zhou, Xinmin ^{[1
,2
]}

Wang, Jingbo ^{[1
,2
]}

Han, Ying ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, Natl Clin Res Ctr Digest Dis, State Key Lab Canc Biol, Xian, Shaanxi, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp Digest Dis, Xian, Shaanxi, Peoples R China

[3] Fourth Mil Med Univ, Xijing Hosp, Div Ultrasonog, Xian, Shaanxi, Peoples R China

[4] Fourth Mil Med Univ, Xijing Hosp, Div Psychiat, Xian, Shaanxi, Peoples R China

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

中国国家自然科学基金;

关键词：

PHENOTYPIC-EXPRESSION; AUTOPHAGIC VACUOLES; STORAGE DISEASE; LAMP-2; CARDIOMYOPATHY; MATURATION; FEATURES; FOCUS; LEADS;

D O I：

10.1038/s41598-018-24351-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Lamp2(y/-) rats also displayed abnormal behaviours in the open field and fear conditioning tests. Notably, Lamp(2y/-) 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.

引用

页数：9

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