State Key Laboratory of Cancer Biology, National Clinical Research Centre for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, China.
Division of Ultrasonography, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Sci Rep. 2018 May 2;8(1):6932. doi: 10.1038/s41598-018-24351-w.
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 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 rats also displayed abnormal behaviours in the open field and fear conditioning tests. Notably, Lamp2 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.
丹诺病（DD）是由溶酶体相关膜蛋白 2（LAMP2）缺失或功能障碍引起的。尽管 Lamp2 缺陷小鼠和 DD 患者具有相似的特征，但这些小鼠存在明显的局限性，且与临床情况不符。本文的目的是概述 Lamp2 缺陷大鼠的特征，并将该模型与目前可用的 DD 小鼠模型进行对比。Lamp2 大鼠的一些血清酶基线水平升高，同时在 8 周时出现高胆固醇血症和高血糖症。超声心动图显示 IVSd（1.500±0.071 比 2.200±1.147，P<0.01）和 LVPWd（1.575±0.063 比 1.850±0.029，P<0.01）明显增加，GCS（-13.20±0.4814 比-6.954±0.665）和 GRS（21.42±1.807 比 7.788±0.114）急剧下降。同时，心脏组织中可见大量肌细胞破坏、肥大的肌纤维、间质纤维化和微血管增生。Lamp2 大鼠在旷场和恐惧条件反射测试中也表现出异常行为。值得注意的是，Lamp2 大鼠还表现出其他系统功能障碍，如视网膜病变、慢性肾损伤和不育。基于这些结果，Lamp2 缺陷大鼠在发病和多系统损伤方面与 DD 患者更为相似，而不是与小鼠模型相似，这些大鼠可作为 DD 的一种有价值的动物模型。
