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Establishment of basal cell carcinoma animal model in Chinese tree shrew (Tupaia belangeri chinensis)

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Zoological Research 2017年第4期38卷 180-190页

作者： Li-Ping Jiang Qiu-Shuo Shen Cui-Ping Yang Yong-Bin Chen key laboratory of animal models and human disease mechanisms Kunming Institute of Zoology Chinese Academy of Sciences Kunming College of Life Science University of Chinese Academy of Sciences

Basal cell carcinoma （BCC） is the most common skin cancer worldwide, with incidence rates continuing to increase. Ultraviolet radiation is the major environmental risk factor and dysregulation of the Hedgehog （Hh） signaling pathway has been identified in most BCCs. The treatment of locally advanced and metastatic BBCs is still a challenge and requires a better animal model than the widely used rodents for drug development and testing. Chinese tree shrews （Tupaia belangeri chinensis） are closely related to primates, bearing many physiological and biochemical advantages over rodents for characterizing human diseases. Here, we successfully established a Chinese tree shrew BCC model by infecting tail skins with lentiviral SmoA1, an active form of Smoothened （Smo） used to constitutively activate the Hh signaling pathway. The pathological characteristics were verified by immunohistochemical analysis. Interestingly, BCC progress was greatly enhanced by the combined usage of lenUviral SmoA1 and shRNA targeting Chinese tree shrew p53. This work provides a useful animal model for further BCC studies and future

关键词： Chinese lree shrew Basal cell carcinoma Hedgehog

Avoidance of potentially harmful food cannot be socially transmitted between rats

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Zoological Research 2014年第4期35卷 256-261页

作者： Liang JING Qi-Xin ZHOU Lin XU laboratory of Learning and Memory Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan ProvinceKunming Institute of Zoology University of Chinese Academy of Sciences

The social transmission of food preferences （STFP） is a behavioural task of olfactory memory, in which an observer rat learns safe food odours from a demonstrator rat, and shows preference for this odour in a subsequent choice test. However, previous studies have failed to detect the transmission of information about food study, we tested how demonstrators＇ health affects the exchange of of potential danger and food aversion using STFP test. In this odour information and whether observers can learn danger information from an unhealthy demonstrator. As expected, the observer rat formed an odour preference after interacting with a demonstrator rat that had just eaten food containing a new odour, however, odour preference rather than aversion was also formed after interacting with a demonstrator rat injected with LiC1 （used to induce gastric malaise）. Furthermore, anaesthetized demonstrator rats and half-anaesthetized demonstrator rats, which showed obvious motor deficits suggesting an unhealthy state, also socially transmitted food preferences to observers. These results suggest that the social transmission of food preferences task is independent of a demonstrators＇ health, and that information about dangerous foods cannot be transmitted using this behavioural task.

关键词： Diet selection Rats Social learning Social transmission of food preference Food aversion

Non-human primate models in drug addiction deserve more attention

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Zoological Research 2014年第3期35卷 172-173页

作者： Jian-Hong WANG key laboratory of animal models and human disease mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology

Dear Editor, The process of relapse involves firm or aberrant memories of environmental cues associated with drug craving or addiction. To date, it is not known where these memories are stored in the brain, what kinds of regulatory biological factors or molecules are involved, nor why it is so difficult to stop addiction psychologically. Currently, rodent animal models, such as the self-administration and conditioning place preference / aversion paradigm are still widely used in the studies of drug withdrawal syndromes or drug-associate memories. However, the differences between humans and rodents--particularly in terms of genetics, and pathology and pharmacology--have significantly limited the application of further studies on this topic. Essentially, rodents lack the longterm or life-time memories humans possess and lose their drug-associated memory only after a few weeks of withdrawal.

关键词： Non-human primate models in drug addiction deserve more attention PFC

Why do we study animal toxins?

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Zoological Research 2015年第4期36卷 183-221页

作者： Yun ZHANG key laboratory of animal models and human disease mechanisms of The Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences

Venom （toxins） is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides （TLPs）. We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins.

关键词： Toxins Survival competition Evolution disease mechanism Drug development

The 3rd Symposium on animal models of Primates——The Application of Non-human Primates to Basic Research and Translational Medicine

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Journal of Genetics and Genomics 2015年第6期42卷 339-341页

作者： Yong-Gang Yao Yong-Bin Chen Bin Liang key laboratory of animal models and human disease mechanisms of the Chinese Academy of Sciences & Yunnan Province and Kunming Primate Research CenterKunming Institute of ZoologyChinese Academy of Sciences

In order to understand the fundamental questions of the biology of life and to duplicate the pathogenesis of human diseases, animal models using different experimental animals, such as rodents, Drosophila, Caenorhabditis elegans, and zebrafish, have been established and used widely for many decades. The controllability of environmental conditions, the high reproducibility, the ease of scale and the comparability of results, as well as the ability to use different standards for ethical protocols, all make an animal model the ideal tool for carrying out studies on human diseases and the development of novel pharmaceuticals and new therapies （Xue et al., 2014）. An ideal animal model should reflect the complete spectra of a specific human disease, with similar features on the following key issues：（1） genetic basis; （2） anatomy and physiology; （3） pathological response（s） and underlying mechanism（s）; （4） phenotypic endpoints as clinical studies; （5） responsiveness to known drugs with clinical efficacy; and （6） prediction of clinical efficacy （McGonigle and Ruggeri, 2014）.

关键词： The 3rd Symposium on animal models of Primates The Application of Non-human Primates to Basic Research and Translational Medicine

The big bang of genome editing technology: development and application of the CRISPR/Cas9 system in disease animal models

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Zoological Research 2016年第4期37卷 191-204页

作者： Ming SHAO Tian-Rui XU Ce-Shi CHEN Faculty of Life Science and Technology Kunming University of Science and Technology key laboratory of animal models and human disease mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences

Targeted genome editing technology has been widely used in biomedical studies. The CRISPR- associated RNA-guided endonuclease Cas9 has become a versatile genome editing tool. The CRISPR/Cas9 system is useful for studying gene function through efficient knock-out, knock-in or chromatin modification of the targeted gene loci in various cell types and organisms. It can be applied in a number of fields, such as genetic breeding, disease treatment and gene functional investigation In this review, we introduce the most recent developments and applications, the challenges, and future directions of Cas9 in generating disease animal model. Derived from the CRISPR adaptive immune system of bacteria, the development trend of Cas9 will inevitably fuel the vital applications from basic research to biotechnology and bio- medicine.

关键词： CRISPR/Cas9 animal models Genetherapy

Preparation and Characterization of Three Monoclonal Antibodies against HIV-1 p24 Capsid Protein

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Cellular & Molecular Immunology 2007年第3期4卷 203-208页

作者： Guangjie Liu Jianping Wang Jianchun Xiao Zhiwei Zhao Yongtang Zheng laboratory of Molecular Immunopharmacology Key Laboratory of Animal Models and Human Disease Mechanisms Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China key laboratory of Conservation and Utilization for Bio-resources Yunnan University Kunming Yunnan 650091 China

HIV-1 p24 detection provides a means to aid the early diagnosis of HIV-1 infection, track the progression of disease and assess the efficacy of antiretroviral therapy. In the present study, three monoclonal antibodies （mAbs） p3JB9, p5F1 and p6F4 against HIV-1 p24 were generated. All mAbs could detect p24 of HIV-1ⅢB, HIV-1Ada-M, HIV-174v mAbs p5F1 and p6F4 could detect HIV-1KM018, while p3JB9 could not. Three mAbs did not react with HIV-2ROD, HIV-2CBL-20 and SIVagmTYO-1. The recognized epitope of p5F1 was located on the Gag amino acid region DCKTILKALGPAATLEEMMTAC. The p5F1 was used to establish a modified sandwich ELISA with rabbit anti-p24 serum and showed good specificity and high sensitivity, which has been used to measure HIV-1 p24 antigen levels in research. Cellular ＆ Molecular Immunology.

关键词： monoclonal antibody HIV-1 p24 epitope ELISA

Phenotype and Function of Monocyte-Derived Dendritic Cells from Chinese Rhesus Macaques

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Cellular & Molecular Immunology 2009年第3期6卷 159-165页

作者： Houjun Xia Hongliang Liu Gaohong Zhang Yongtang Zheng key laboratory of animal models and human disease mechanisms of Chinese Academy of Sciences ＆ Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China Graduate School of the Chinese Academy of Sciences Beijing 100039 China

Dendritic cells （DCs） play a pivotal role in linking the innate immunity and acquired immunity in responses to pathogen. Non-human primates such as Chinese Rhesus Macaque （CRM） are the favorable models for preclinical study of potential therapeutic drugs, vaccines and mechanisms of human diseases. However, the phenotypical characterization of monocyte-derived dendritic cells （MDDCs） from CRM has not been elucidated. Monocytes from CRM were cultured with GM-CSF and IL-4 in RPMI-1640. Six days later, these cells were differentiated with typical dendritical morphology. CDllc and DC-SIGN were highly expressed. The immature MDDCs expressed the low levels of CD25, CD80, CD83, moderate CD40, CD86, and high MHC. After stimulation, the mature MDDCs increased expression of mature molecules CD25 and CD83, co-stimulatory molecules such as CD80, CD86 and CD40, and kept a high level of MHC. The capacity of endocytosis decreased with maturation. The mature MDDCs have strong ability of inducing allogeneic T cell proliferation and producing IL-12. In conclusion, we have characterized the phenotype and ultimate function of MDDCs from CRM for the first time.

关键词： monocyte-derived dendritic cell animal model Chinese Rhesus Macaque

Protease-activated receptor(PAR)1, PAR2 and PAR4 expressions in esophageal squamous cell carcinoma

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Zoological Research 2014年第5期35卷 420-425页

作者： Si-Man LI Ping JIANG Yang XIANG Wei-Wei WANG Yue-Chun ZHU Wei-Yang FENG Shu-De LI Guo-Yu YU Kunming Medical University key laboratory of animal models and human disease mechanisms of the Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Third Affiliated Hospital of Kunming Medical University Department of Thoracic Surgery

Here,we used reverse transcription-PCR(RT-PCR) and western blot to detect protease-activated receptor(PAR) 1,PAR 2 and PAR 4 expression in cancer tissues and cell lines of esophageal squamous cell carcinoma,and investigated the co-relationship between PAR expression and clinic-pathological data for esophageal *** methylation of PAR4 gene promoter involved in esophageal carcinoma was also *** comparing the mRNA expressions of normal esophageal tissue and human esophageal epithelial cells(HEEpiC),we found that among the 28 cases of esophageal squamous cell carcinoma,PAR1(60%) and PAR2(71%) were elevated in 17 and 20 cases,respectively,and PAR4(68%) expression was lowered in 19 ***,in human esophageal squamous cells(TE-1 and TE-10),PAR1 and PAR2 expression was increased but PAR4 was *** with clinical data,the expression of PAR1 in poorly differentiated(P=0.016) and middle and lower parts of the esophagus(P=0.016) was higher; expression of PAR4 in poorly differentiated carcinoma was lower(P=0.049).Regarding TE-1 and TE-10 protein expression,we found that in randomized esophageal carcinoma,PAR1(P=0.027) and PAR2(P=0.039) expressions were increased,but lowered for PAR4(P=0.0001).In HEEpiC,TE-1,TE-10,esophageal and normal esophagus tissue samples(case No.7),the frequency of methylation at the 19 CpG loci of PAR4 was 35.4%,95.2%,83.8%,62.6% and 48.2%,*** results indicate that the expression of PAR1 and PAR2 in esophageal squamous cell carcinoma is increased but PAR4 is *** of the promoter of the PAR4 gene may contribute to reduced expression of PAR4 in esophageal squamous cell carcinoma.

关键词： PAR1 PAR2 PAR4 Esophageal squamous cell carcinoma PCR Western Blot Methylation