Volume 38 Issue 3
May  2017
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Yong-Gang Yao. Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?. Zoological Research, 2017, 38(3): 118-126. doi: 10.24272/j.issn.2095-8137.2017.032
Citation: Yong-Gang Yao. Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?. Zoological Research, 2017, 38(3): 118-126. doi: 10.24272/j.issn.2095-8137.2017.032

Creating animal models, why not use the Chinese tree shrew (Tupaia belangeri chinensis)?

doi: 10.24272/j.issn.2095-8137.2017.032
Funds:  This study was supported by the grant of the National Natural Science Foundation of China (NSFC U1402224) and the Chinese Academy of Sciences (CAS zsys-02)
More Information
  • Corresponding author: Yong-Gang Yao,E-mail:yaoyg@mail.kiz.ac.cn
  • Received Date: 2017-02-08
  • Rev Recd Date: 2017-04-10
  • Publish Date: 2017-05-18
  • The Chinese tree shrew (Tupaia belangeri chinensis), a squirrel-like and rat-sized mammal, has a wide distribution in Southeast Asia, South and Southwest China and has many unique characteristics that make it suitable for use as an experimental animal. There have been many studies using the tree shrew (Tupaia belangeri) aimed at increasing our understanding of fundamental biological mechanisms and for the modeling of human diseases and therapeutic responses. The recent release of a publicly available annotated genome sequence of the Chinese tree shrew and its genome database (www.treeshrewdb.org) has offered a solid base from which it is possible to elucidate the basic biological properties and create animal models using this species. The extensive characterization of key factors and signaling pathways in the immune and nervous systems has shown that tree shrews possess both conserved and unique features relative to primates. Hitherto, the tree shrew has been successfully used to create animal models for myopia, depression, breast cancer, alcohol-induced or non-alcoholic fatty liver diseases, herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV) infections, to name a few. The recent successful genetic manipulation of the tree shrew has opened a new avenue for the wider usage of this animal in biomedical research. In this opinion paper, I attempt to summarize the recent research advances that have used the Chinese tree shrew, with a focus on the new knowledge obtained by using the biological properties identified using the tree shrew genome, a proposal for the genome-based approach for creating animal models, and the genetic manipulation of the tree shrew. With more studies using this species and the application of cutting-edge gene editing techniques, the tree shrew will continue to be under the spot light as a viable animal model for investigating the basis of many different human diseases.
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  • [1]
    Amako Y, Tsukiyama-Kohara K, Katsume A, Hirata Y, Sekiguchi S, Tobita Y, Hayashi Y, Hishima T, Funata N, Yonekawa H, Kohara M. 2010. Pathogenesis of hepatitis C virus infection in Tupaia belangeri. Journal of Virology, 84(1):303-311.
    Barbalat R, Ewald SE, Mouchess ML, Barton GM. 2011. Nucleic acid recognition by the innate immune system. Annual Review of Immunology, 29(1):185-214.
    Bennett AJ, Panicker S. 2016. Broader impacts:international implications and integrative ethical consideration of policy decisions about US chimpanzee research. American Journal of Primatology, 78(12):1282-1303.
    Cao J, Yang EB, Su JJ, Li Y, Chow P. 2003. The tree shrews:adjuncts and alternatives to primates as models for biomedical research. Journal of Medical Primatology, 32(3):123-130.
    Cong L, Ran FA, Cox D, Lin SL, Barretto R, Habib N, Hsu PD, Wu XB, Jiang WY, Marraffini LA, Zhang F. 2013. Multiplex genome engineering using CRISPR/Cas systems. Science, 339(6121):819-823.
    Darai G, Schwaier A, Komitowski D, Munk K. 1978. Experimental infection of Tupaia belangeri (tree shrews) with herpes simplex virus types 1 and 2. Journal of Infectious Diseases, 137(3):221-226.
    Elliot OS, Elliot MW, Lisco H. 1966. Breast cancer in a tree shrew (Tupaia glis). Nature, 211(5053):1105.
    Fan Y, Huang ZY, Cao CC, Chen CS, Chen YX, Fan DD, He J, Hou HL, Hu L, Hu XT, Jiang XT, Lai R, Lang YS, Liang B, Liao SG, Mu D, Ma YY, Niu YY, Sun XQ, Xia JQ, Xiao J, Xiong ZQ, Xu L, Yang L, Zhang Y, Zhao W, Zhao XD, Zheng YT, Zhou JM, Zhu YB, Zhang GJ, Wang J, Yao YG. 2013. Genome of the Chinese tree shrew. Nature Communications, 4:1426.
    Fan Y, Yao YG. 2014. Chapter 3. Characteristics of the genome of the Chinese tree shrew. In:Zheng YT, Yao YG, Xu L. Basic Biology and Disease Models of Tree Shrews. Kunming:Yunnan Science and Technology Press, 32-75. (in Chinese)
    Fan Y, Yu D, Yao YG. 2014a. Tree shrew database (TreeshrewDB):a genomic knowledge base for the Chinese tree shrew. Scientific Reports, 4:7145.
    Fan Y, Yu DD, Yao YG. 2014b. Positively selected genes of the Chinese tree shrew (Tupaia belangeri chinensis) locomotion system. Zoological Research, 35(3):240-248.
    Fang H, Sun YJ, Lv YH, Ni RJ, Shu YM, Feng XY, Wang Y, Shan QH, Zu YN, Zhou JN. 2016. High activity of the stress promoter contributes to susceptibility to stress in the tree shrew. Scientific Reports, 6:24905.
    Fitzpatrick D. 1996. The functional organization of local circuits in visual cortex:insights from the study of tree shrew striate cortex. Cerebral Cortex, 6(3):329-341.
    Franco NH. 2013. Animal experiments in biomedical research:a historical perspective. Animals, 3(1):238-273.
    Fuchs E. 2005. Social stress in tree shrews as an animal model of depression:an example of a behavioral model of a CNS disorder. CNS Spectrums, 10(3):182-190.
    Ge GZ, Xia HJ, He BL, Zhang HL, Liu WJ, Shao M, Wang CY, Xiao J, Ge F, Li FB, Li Y, Chen CS. 2016. Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution. International Journal of Cancer, 138(3):642-651.
    Grillner S, Ip N, Koch C, Koroshetz W, Okano H, Polachek M, Poo MM, Sejnowski TJ. 2016. Worldwide initiatives to advance brain research. Nature Neuroscience, 19(9):1118-1122.
    Guo XY, Li XJ. 2015. Targeted genome editing in primate embryos. Cell Research, 25(7):767-768.
    Hsu PD, Lander ES, Zhang F. 2014. Development and applications of CRISPR-Cas9 for genome engineering. Cell, 157(6):1262-1278.
    Hunt DM, Dulai KS, Cowing JA, Julliot C, Mollon JD, Bowmaker JK, Li WH, Hewett-Emmett D. 1998. Molecular evolution of trichromacy in primates. Vision Research, 38(21):3299-3306.
    Khani A, Rainer G. 2012. Recognition memory in tree shrew (Tupaia belangeri) after repeated familiarization sessions. Behavioural Processes, 90(3):364-371.
    Knight A. 2008. The beginning of the end for chimpanzee experiments? Philosophy, Ethics, and Humanities in Medicine, 3:16.
    Lee KS, Huang XY, Fitzpatrick D. 2016. Topology of ON and OFF inputs in visual cortex enables an invariant columnar architecture. Nature, 533(7601):90-94.
    Li CH, Yan LZ, Ban WZ, Tu Q, Wu Y, Wang L, Bi R, Ji S, Ma YH, Nie WH, Lv LB, Yao YG, Zhao XD, Zheng P. 2017. Long-term propagation of tree shrew spermatogonial stem cells in culture and successful generation of transgenic offspring. Cell Research, 27(2):241-252.
    Li LH, Li ZR, Wang EL, Yang R, Xiao Y, Han HB, Lang FC, Li X, Xia YJ, Gao F, Li QH, Fraser NW, Zhou JM. 2016. Herpes simplex virus 1 infection of tree shrews differs from that of mice in the severity of acute infection and viral transcription in the peripheral nervous system. Journal of Virology, 90(2):790-804.
    Li RX, Xu W, Wang Z, Liang B, Wu JR, Zeng R. 2012. Proteomic characteristics of the liver and skeletal muscle in the Chinese tree shrew(Tupaia belangeri chinensis). Protein & Cell, 3(9):691-700.
    Lin JN, Chen GF, Gu L, Shen YF, Zheng MZ, Zheng WS, Hu XJ, Zhang XB, Qiu Y, Liu XQ, Jiang CZ. 2014. Phylogenetic affinity of tree shrews to Glires is attributed to fast evolution rate. Molecular Phylogenetics and Evolution, 71:193-200.
    Luo X, Li M, Su B. 2016. Application of the genome editing tool CRISPR/Cas9 in non-human primates. Zoological Research, 37(4):214-219.
    MacEvoy SP, Tucker TR, Fitzpatrick D. 2009. A precise form of divisive suppression supports population coding in the primary visual cortex. Nature Neuroscience, 12(5):637-645.
    McGonigle P, Ruggeri B. 2014. Animal models of human disease:challenges in enabling translation. Biochemical Pharmacology, 87(1):162-171.
    Mei Y, Wang Y, Chen HQ, Sun ZS, Ju XD. 2016. Recent progress in CRISPR/Cas9 technology. Journal of Genetics and Genomics, 43(2):63-75.
    Mooser F, Bosking WH, Fitzpatrick D. 2004. A morphological basis for orientation tuning in primary visual cortex. Nature Neuroscience, 7(8):872-879.
    Muly EC, Fitzpatrick D. 1992. The morphological basis for binocular and ON/OFF convergence in tree shrew striate cortex. Journal of Neuroscience, 12(4):1319-1334.
    Nair J, Topka M, Khani A, Isenschmid M, Rainer G. 2014. Tree shrews(Tupaia belangeri) exhibit novelty preference in the novel location memory task with 24-h retention periods. Frontiers in Psychology, 5:303.
    Ni RJ, Shu YM, Wang J, Yin JC, Xu L, Zhou JN. 2014. Distribution of vasopressin, oxytocin and vasoactive intestinal polypeptide in the hypothalamus and extrahypothalamic regions of tree shrews. Neuroscience, 265:124-136.
    Ni RJ, Shu YM, Luo PH, Fang H, Wang Y, Yao L, Zhou JN. 2015. Immunohistochemical mapping of neuropeptide Y in the tree shrew brain. Journal of Comparative Neurology, 523(3):495-529.
    Niu YY, Shen B, Cui YQ, Chen YC, Wang JY, Wang L, Kang Y, Zhao XY, Si W, Li W, Xiang AP, Zhou JK, Guo XJ, Bi Y, Si CY, Hu B, Dong GY, Wang H, Zhou ZM, Li TQ, Tan T, Pu XQ, Wang F, Ji SH, Zhou Q, Huang XX, Ji WZ, Sha JH. 2014. Generation of gene-modified cynomolgus monkey via Cas9/RNA-mediated gene targeting in one-cell embryos. Cell, 156(4):836-843.
    O'Leary MA, Bloch JI, Flynn JJ, Gaudin TJ, Giallombardo A, Giannini NP, Goldberg SL, Kraatz BP, Luo ZX, Meng J, Ni X, Novacek MJ, Perini FA, Randall ZS, Rougier GW, Sargis EJ, Silcox MT, Simmons NB, Spaulding M, Velazco PM, Weksler M, Wible JR, Cirranello AL. 2013. The placental mammal ancestor and the post-K-Pg radiation of placentals. Science, 339(6120):662-667.
    Pawlik M, Fuchs E, Walker LC, Levy E. 1999. Primate-like amyloid-β sequence but no cerebral amyloidosis in aged tree shrews. Neurobiology of Aging, 20(1):47-51.
    Peng YZ, Ye ZZ, Zou RJ, Wang YX, Tian BP, Ma YY, Shi LM. 1991. Biology of Chinese Tree Shrews. Kunming:Yunnan Science and Technology Press.(in Chinese)
    Petruzziello F, Fouillen L, Wadensten H, Kretz R, Andren PE, Rainer G, Zhang XZ. 2012. Extensive characterization of Tupaia belangeri neuropeptidome using an integrated mass spectrometric approach. Journal of Proteome Research, 11(2):886-896.
    Pryce CR, Fuchs E. 2017. Chronic psychosocial stressors in adulthood:studies in mice, rats and tree shrews. Neurobiology of Stress, 6:94-103.
    Shao M, Xu TR, Chen CS. 2016. The big bang of genome editing technology:development and application of the CRISPR/Cas9 system in disease animal models. Zoological Research, 37(4):191-204.
    Song S, Liu L, Edwards SV, Wu SY. 2012. Resolving conflict in eutherian mammal phylogeny using phylogenomics and the multispecies coalescent model. Proceedings of the National Academy of Sciences of the United States of America, 109(37):14942-14947.
    Su JJ, Yan QR, Gan YQ, Zhou DN, Huang DR, Huang GH. 1987. Experimental infection of human hepatitis B virus (HBV) in adult tree shrews. Chinese Journal of Pathology, 16(2):103-106. (in Chinese)
    Takeuchi O, Akira S. 2010. Pattern recognition receptors and inflammation. Cell, 140(6):805-820.
    van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O'Collins V, Macleod MR. 2010. Can animal models of disease reliably inform human studies? PLoS Medicine, 7(3):e1000245.
    Van Hooser SD, Roy A, Rhodes HJ, Culp JH, Fitzpatrick D. 2013. Transformation of receptive field properties from lateral geniculate nucleus to superficial V1 in the tree shrew. Journal of Neuroscience, 33(28):11494-11505.
    Veit J, Bhattacharyya A, Kretz R, Rainer G. 2011. Neural response dynamics of spiking and local field potential activity depend on CRT monitor refresh rate in the tree shrew primary visual cortex. Journal of Neurophysiology, 106(5):2303-2313.
    Veit J, Bhattacharyya A, Kretz R, Rainer G. 2014. On the relation between receptive field structure and stimulus selectivity in the tree shrew primary visual cortex. Cerebral Cortex, 24(10):2761-2771.
    Walter E, Keist R, Niederöst B, Pult I, Blum HE. 1996. Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo. Hepatology, 24(1):1-5.
    Wang LR, Shao YJ, Guan YT, Li L, Wu LJ, Chen FR, Liu MZ, Chen HQ, Ma YL, Ma XY, Liu MY, Li DL. 2015. Large genomic fragment deletion and functional gene cassette knock-in via Cas9 protein mediated genome editing in one-cell rodent embryos. Scientific Reports, 5:17517.
    Xia HJ, Wang CY, Zhang HL, He BL, Jiao JL, Chen CS. 2012. Characterization of spontaneous breast tumor in tree shrews (Tupaia belangeri chinenesis). Zoological Research, 33(1):55-59.
    Xia HJ, He BL, Wang CY, Zhang HL, Ge GZ, Zhang YX, Lv LB, Jiao JL, Chen CS. 2014. PTEN/PIK3CA genes are frequently mutated in spontaneous and medroxyprogesterone acetate-accelerated 7, 12-dimethylbenz(a)anthracene-induced mammary tumours of tree shrews. European Journal of Cancer, 50(18):3230-3242.
    Xing HJ, Jia K, He J, Shi CZ, Fang MX, Song LL, Zhang P, Zhao Y, Fu JN, Li SJ. 2015. Establishment of the tree shrew as an alcohol-induced Fatty liver model for the study of alcoholic liver diseases. PLoS One, 10(6):e0128253.
    Xu L, Chen SY, Nie WH, Jiang XL, Yao YG. 2012. Evaluating the phylogenetic position of Chinese tree shrew (Tupaia belangeri chinensis) based on complete mitochondrial genome:implication for using tree shrew as an alternative experimental animal to primates in biomedical research. Journal of Genetics and Genomics, 39(3):131-137.
    Xu L, Fan Y, Jiang XL, Yao YG. 2013a. Molecular evidence on the phylogenetic position of tree shrews. Zoological Research, 34(2):70-76. (in Chinese)
    Xu L, Zhang Y, Liang B, Lü LB, Chen CS, Chen YB, Zhou JM, Yao YG. 2013b. Tree shrews under the spot light:emerging model of human diseases. Zoological Research, 34(2):59-69. (in Chinese)
    Xu L, Yu DD, Fan Y, Peng L, Wu Y, Yao YG. 2016. Loss of RIG-I leads to a functional replacement with MDA5 in the Chinese tree shrew. Proceedings of the National Academy of Sciences of the United States of America, 113(39):10950-10955.
    Xu XP, Chen HB, Cao XM, Ben KL. 2007. Efficient infection of tree shrew(Tupaia belangeri) with hepatitis C virus grown in cell culture or from patient plasma. Journal of General Virology, 88(9):2504-2512.
    Yamashita A, Fuchs E, Taira M, Hayashi M. 2010. Amyloid beta (Aβ) protein-and amyloid precursor protein (APP)-immunoreactive structures in the brains of aged tree shrews. Current Aging Science, 3(3):230-238.
    Yamashita A, Fuchs E, Taira M, Yamamoto T, Hayashi M. 2012. Somatostatin-immunoreactive senile plaque-like structures in the frontal cortex and nucleus accumbens of aged tree shrews and Japanese macaques. Journal of Medical Primatology, 41(3):147-157.
    Yan H, Zhong GC, Xu GW, He WH, Jing ZY, Gao ZC, Huang Y, Qi YH, Peng B, Wang HM, Fu LR, Song M, Chen P, Gao WQ, Ren BJ, Sun YY, Cai T, Feng XF, Sui JH, Li WH. 2012. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife, 1:e00049.
    Yan LZ, Sun B, Lyu LB, Ma YH, Chen JQ, Lin Q, Zheng P, Zhao XD. 2016. Early embryonic development and transplantation in tree shrews. Zoological Research, 37(4):252-258.
    Yan RQ, Su JJ, Huang DR, Gan YC, Yang C, Huang GH. 1996. Human hepatitis B virus and hepatocellular carcinoma I. Experimental infection of tree shrews with hepatitis B virus. Journal of Cancer Research and Clinical Oncology, 122(5):283-288.
    Yao YG, Chen YB, Liang B. 2015. The 3rd symposium on animal models of primates-the application of non-human primates to basic research and translational medicine. Journal of Genetics and Genomics, 42(6):339-341.
    Yu DD, Wu Y, Xu L, Fan Y, Peng L, Xu M, Yao YG. 2016. Identification and characterization of toll-like receptors (TLRs) in the Chinese tree shrew(Tupaia belangeri chinensis). Developmental & Comparative Immunology, 60:127-138.
    Zhang LQ, Zhang ZG, Li YH, Liao SS, Wu XY, Chang Q, Liang B. 2015. Cholesterol induces lipoprotein lipase expression in a tree shrew (Tupaia belangeri chinensis) model of non-alcoholic fatty liver disease. Scientific Reports, 5:15970.
    Zhang LQ, Wu XY, Liao SS, Li YH, Zhang ZG, Chang Q, Xiao RY, Liang B. 2016. Tree shrew (Tupaia belangeri chinensis), a novel non-obese animal model of non-alcoholic fatty liver disease. Biology Open, 5(10):1545-1552.
    Zhang XL, Pang W, Hu XT, Li JL, Yao YG, Zheng YT. 2014. Experimental primates and non-human primate (NHP) models of human diseases in China:current status and progress. Zoological Research, 35(6):447-464.
    Zhao F, Guo XL, Wang YJ, Liu J, Lee WH, Zhang Y. 2014. Drug target mining and analysis of the Chinese tree shrew for pharmacological testing. PLoS One, 9(8):e104191.
    Zhao XP, Tang ZY, Klumpp B, Wolff-Vorbeck G, Barth H, Levy S, von Weizsäcker F, Blum HE, Baumert TF. 2002. Primary hepatocytes of Tupaia belangeri as a potential model for hepatitis C virus infection. Journal of Clinical Investigation, 109(2):221-232.
    Zheng YT, Yao YG, Xu L. 2014. Basic Biology and Disease Models of Tree Shrews. Kunming:Yunnan Science and Technology Press, 1-475. (in Chinese)
    Zhou XM, Sun FM, Xu SX, Yang G, Li M. 2015. The position of tree shrews in the mammalian tree:comparing multi-gene analyses with phylogenomic results leaves monophyly of Euarchonta doubtful. Integrative Zoology, 10(2):186-198.
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