Does the Genetic Feature of the Chinese Tree Shrew (Tupaia belangeri chinensis) Support Its Potential as a Viable Model for Alzheimer’s Disease Research?

Article type: Research Article

Authors: Fan, Yu^{a; 1} | Luo, Rongcan^{a; b; 1} | Su, Ling-Yan^{a; b} | Xiang, Qun^a | Yu, Dandan^a | Xu, Ling^a | Chen, Jia-Qi^c | Bi, Rui^a | Wu, Dong-Dong^d | Zheng, Ping^{c; d; e; *} | Yao, Yong-Gang^{a; b; c; f; *}

Affiliations: [a] Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan, China | [b] Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan, China | [c] Kunming Primate Research Center of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China | [d] State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China | [e] Yunnan Key Laboratory of Animal Reproduction, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China | [f] Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China

Correspondence: [*] Correspondence to: Dr. Yong-Gang Yao, Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China. Tel./Fax: +86 871 65180085; E-mail: [email protected] and Dr. Ping Zheng, Kunming Primate Research Center of the Chinese Academy of Sciences, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China. E-mail: [email protected].

Note: [†] These authors contributed equally to this work.

Abstract: Alzheimer’s disease (AD) is a neurodegenerative disease with increasing incidence across the world and no cure at the present time. An ideal animal model would facilitate the understanding of the pathogenesis of AD and discovery of potential therapeutic targets. The Chinese tree shrew (Tupaia belangeri chinensis) has a closer genetic affinity to primates relative to rodents, and can attain ages of 8 years or older, which represents another advantage for the study of neurodegenerative diseases such as AD compared to primates. Here, we analyzed 131 AD-related genes in the Chinese tree shrew brain tissues based on protein sequence identity, positive selection, mRNA, and protein expression by comparing with those of human, rhesus monkey, and mouse. In particular, we focused on the Aβ and neurofibrillary tangles formation pathways, which are crucial to AD pathogenesis. The Chinese tree shrew had a generally higher sequence identity with human than that of mouse versus human for the AD pathway genes. There was no apparent selection on the tree shrew lineage for the AD-related genes. Moreover, expression pattern of the Aβ and neurofibrillary tangle formation pathway genes in tree shrew brain tissues resembled that of human brain tissues, with a similar aging-dependent effect. Our results provided an essential genetic basis for future AD research using the tree shrew as a viable model.

Keywords: AD pathway, Alzheimer’s disease, animal model, Chinese tree shrews, mRNA expression profiling

DOI: 10.3233/JAD-170594

Journal: Journal of Alzheimer's Disease, vol. 61, no. 3, pp. 1015-1028, 2018