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 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 Lamp2y/- 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.

• Authors: 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
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 6932 (05 02 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 29720683 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Lysosomal-Associated Membrane Protein 2

Topics

• Animals
• Biomarkers
• Cardiomyopathy, Hypertrophic (genetics, metabolism, pathology, physiopathology)
• Disease Models, Animal
• Gene Deletion
• Gene Knockout Techniques
• Glycogen Storage Disease Type IIb (etiology, metabolism, pathology)
• Lysosomal-Associated Membrane Protein 2 (genetics)
• Muscle, Skeletal (metabolism, pathology)
• Rats
• Rats, Transgenic