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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

Neuroprotection by immunomodulatory agents in animal models of Parkinson's disease

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Neural Regeneration Research 2018年第9期13卷 1493-1506页

作者： Bridget Martinez Philip V.Peplow Department of Molecular & Cellular Biology University of CaliforniaMercedCAUSA Department of Medicine St.Georges University School of Medicine Department of Physics and Engineering Los Alamos National Laboratory Department of Anatomy University of Otago

Parkinson’s disease（PD） is an age-related neurodegenerative disease for which the characteristic motor symptoms emerge after an extensive loss of dopamine containing neurons.The cell bodies of these neurons are present in the substantia nigra,with the nerve terminals being in the striatum.Both innate and adaptive immune responses may contribute to dopaminergic neurodegeneration and disease progression is potentially linked to these.Studies in the last twenty years have indicated an important role for neuroinflammation in PD through degeneration of the nigrostriatal dopaminergic pathway.Characteristic of neuroinflammation is the activation of brain glial cells,principally microglia and astrocytes that release various soluble factors.Many of these factors are proinflammatory and neurotoxic and harmful to nigral dopaminergic neurons.Recent studies have identified several different agents with immunomodulatory properties that protected dopaminergic neurons from degeneration and death in animal models of PD.All of the agents were effective in reducing the motor deficit and alleviating dopaminergic neurotoxicity and,when measured,preventing the decrease of dopamine upon being administered therapeutically after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,6-hydroxydopamine,rotenone-lesioning or delivery of adeno-associated virus-α-synuclein to the ventral midbrain of animals.Some of these agents were shown to exert an anti-inflammatory action,decrease oxidative stress,and reduce lipid peroxidation products.Activation of microglia and astrocytes was also decreased,as well as infiltration of T cells into the substantia nigra.Pretreatment with fingolimod,tanshinoine I,dimethyl fumarate,thalidomide,or cocaine-and amphetamine-regulated transcript peptide as a preventive strategy ameliorated motor deficits and nigral dopaminergic neurotoxicity in brain-lesioned animals.Immunomodulatory agents could be used to treat patients with early clinical signs of the disease or potentially even prior to disease onset in those identified

关键词： Parkinson＇s disease immunomodulatory agents neuroprotection inflammation oxidative stress animal models microgliosis astrogliosis

COX-2 in liver,from regeneration to hepatocarcinogenesis:What we have learned from animal models?

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World Journal of Gastroenterology 2010年第12期16卷 1430-1435页

作者： Paloma Martín-Sanz Rafael Mayoral Marta Casado Lisardo Boscá Biomedical Network Center for the Study of Hepatic and Digestive Diseases(CIBERehd) Department of Metabolism and Cell Signaling Institute of Biomedical Research "Alberto Sols"(CSIC-UAM) Department of Pathology and Molecular and Cellular Therapy Institute of Biomedicine of Valencia(IBV-CSIC)

The use of animals lacking genes or expressing genes under the control of cell-specific promoters has signifi cantly increased our knowledge of the genetic and molecular basis of physiopathology,allowing testing of functional hypotheses and validation of biochemical and pharmacologic approaches in order to understand cell function.However,with unexpected frequency,gene knockout animals and,more commonly,animal models of transgenesis give experimental support to even opposite conclusions on gene function.Here we summarize what we learned on the role of cyclooxygenase 2(COX-2) in liver and revise the results obtained in 3 independent models of mice expressing a COX-2 transgene specifi cally in the hepatocyte.Upon challenge with pro-inflammatory stimuli,the animals behave very differently,some transgenic models having a protective effect but others enhancing the injury.In addition,one transgene exerts differential effects on normal liver physiology depending on the transgenic animal model used.

关键词： Cyclooxygenase 2 Prostaglandins Liver diseases Apoptosis Inflammation animal models

Commonly used animal models of non-alcoholic steatohepatitis

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Hepatobiliary & Pancreatic Diseases International 2009年第3期8卷 233-240页

作者： Fan, Jian-Gao Qiao, Liang Univ Hong Kong Queen Mary Hosp Div Gastroenterol & Hepatol Dept Med Hong Kong Hong Kong Peoples R China Shanghai Jiao Tong Univ Xinhua Hosp Dept Gastroenterol Sch Med Shanghai 200092 Peoples R China

BACKGROUND: animal models are an essential tool in non-alcoholic steatohepatitis (NASH) studies. Ideally, such models should reflect the etiology, disease progression, and the established pathology of human NASH. To date, no single animal model displays the range of histopathologic and pathophysiologic features associated with human NASH. The currently available models do not or only partially reflect the real picture of human NASH. In particular, insulin resistance and fibrosing steatohepatitis are rarely reproduced by the currently available models. Consequently, it is necessary to establish NASH models that can best mimic the real etiology, disease progression, and pathogenesis of human NASH. DATA SOURCES: We reviewed the major currently available animal models published in the literature (PubMed) and briefly commented on the pros and cons of these models. RESULT: Three major categories of animal models, genetic, dietary, and combination models, were reviewed and discussed. CONCLUSIONS: animal models are not only useful in revealing the etiology of NASH, but also are important platforms for the assessment of therapeutic strategies. Currently available models do not reflect the full picture of NASH in patients. Better animal models are needed for a full understanding of human NASH and the development of efficient therapies for this condition. (Hepatobiliary Pancreat Dis Int 2009; 8:233-240)

关键词： non-alcoholic fatty liver disease non-alcoholic steatohepatitis animal models

Summary of animal models of myelodysplastic syndrome

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animal models and Experimental Medicine 2021年第1期4卷 71-76页

作者： Weisha Li Mengyuan Li Xingjiu Yang Wenlong Zhang Lin Cao Ran Gao NHC Key Laboratory of Human Disease Comparative Medicine BeijingChina Beijing Engineering Research Center for Experimental animal models of Human Critical Diseases BeijingChina Institute of Laboratory animal Sciences Chinese Academy of Medical Sciences(CAMS)BeijingChina Comparative Medicine Center Peking Union Medical College(PUMC)BeijingChina Beijing Tongren Hospital Affiliated to Capital Medical University BeijingChina

Myelodysplastic syndrome(MDS)is a malignant tumor of the hematological system characterized by long-term,progressive refractory hemocytopenia.In addition,the risk of leukemia is high,and once it develops,the course of acute leukemia is short with poor curative effect.animal models are powerful tools for studying human diseases and are highly effective preclinical platforms.animal models of MDS can accurately show genetic aberrations and hematopoietic clone phenotypes with similar cellular features(such as impaired differentiation and increased apoptosis),and symptoms can be used to assess existing treatments.animal models are also helpful for understanding the pathogenesis of MDS and its relationship with acute leukemia,which helps with the identification of candidate genes related to the MDS phenotype.This review summarizes the current status of animal models used to research myelodysplastic syndrome(MDS).

关键词： animal models Leukemia myelodysplastic syndrome(MDS)

animal models for hepatocellular carcinoma arising from alcoholic and metabolic liver diseases

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Hepatoma Research 2020年第2期6卷 39-54页

作者： Ken Liu Jinbiao Chen Geoffrey W.McCaughan A.W.Morrow Gastroenterology and Liver Centre Royal Prince Alfred HospitalSydneyNSW 2050Australia Sydney Medical School University of SydneySydneyNSW 2050Australia Liver Injury and Cancer Program Centenary InstituteSydneyNSW 2050Australia

Hepatocellular carcinoma (HCC) is a major and increasing cause of clinical and economic burden worldwide. Now that there are effective therapies to control or eradicate viral aetiologies, the landscape of HCC is changing with alcoholic and metabolic liver diseases becoming major catalysts. The pathogenesis of HCC is complex and incompletely understood, hampering improvements in therapy. animal models are essential tools for advancing study on the cellular and molecular processes in HCC and for screening potential novel therapies. Many models of hepatocarcinogenesis have been established using various methods including genetic engineering, chemotoxic agents and dietary manipulation to direct implantation of tumour cells. However, none of these can accurately replicate all features found in human diseases. In this review, we provide an overview of different mouse models of HCC with a particular focus on cancer arising from alcoholic liver disease, non-alcoholic fatty liver disease and hereditary haemochromatosis. We also highlight their strengths and limitations and provide perspectives for future study.

关键词： Hepatocellular carcinoma animal models mouse models non-alcoholic fatty liver disease alcohol haemochromatosis

Role of T Cells in Viral and Immune-mediated Myocarditis

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Cardiology Discovery 2024年第1期4卷 43-54页

作者： Chunyan Cheng Anna Baritussio Andrea Silvio Giordani Renzo Marcolongo Alida L.P.Caforio Sabino Iliceto Department of Cardiovascular Medicine Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510080China Cardiology Unit Department of Cardiac Thoracic Vascular Sciences and Public HealthUniversity of PadovaVia Giustiniani2Padova 35128Italy

Myocarditis is characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function with a heterogeneous etiology. Both viral- and myosin-induced myocarditis experimental models are used to mimic myocarditis in humans. Here, coxsackie virus B3-induced and non-virus-induced myocarditis models and data obtained in clinical studies were reviewed. Experimental murine myocarditis following immunization with α-myosin together with complete Freund adjuvant represents the classical immune-mediated model. T helper 1 (Th1) and Th2 pathways and important cytokines are involved in the autoimmunity of myocarditis, and the dynamic balance between Th17 and regulatory T cell seems to have an important role in the process of myocarditis. The purpose of this review is to summarize the existing understanding of the immunological mechanisms underlying myocarditis and exploring gaps in knowledge in both animal and human studies, since these mechanistic insights are a critical requirement for the development of novel therapeutic and vaccination strategies.

关键词： Myocarditis Immunity T cells animal models Clinical study

Establishment of drug-resistant HBV small-animal models by hydrodynamic injection

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Acta Pharmaceutica Sinica B 2014年第4期4卷 270-276页

作者： Junjun Cheng Yanxing Han Jian-Dong Jiang State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China

In antiviral therapy of hepatitis B virus(HBV)infection,drug resistance remains a huge obstacle to the long-term effectiveness of nucleoside/tide analogs(NAs).Primary resistance mutation(rtM204V)contributes to lamivudine(LAM)-resistance,and compensatory mutations(rtL180M and rtV173L)restore viral fitness and increase replication efficiency.The evaluation of new anti-viral agents against drug-resistant HBV is limited by the lack of available small-animal models.We established LAM-resistance HBV replication mice models based on clinical LAM-resistant HBV mutants.Double(rtM204VþrtL180M)or triple(rtM204VþrtL180MþrtV173L)lamivudine-resistant mutations were introduced into HBV expression vector,followed by hydrodynamic injection into tail vein of NOD/SCID mice.Viremia was detected on days 5,9,13 and 17 and liver HBV DNA was detected on day 17 after injection.The serum and liver HBV DNA levels in LAM-resistant model carrying triple mutations are the highest among the models.Two NAs,LAM and entecavir(ETV),were used to test the availability of the models.LAM and ETV inhibited viral replication on wild-type model.LAM was no longer effective on LAM-resistant models,but ETV retains a strong activity.Therefore,these models can be used to evaluate anti-viral agents against lamivudine-resistance,affording new opportunities to establish other drug-resistant HBV small-animal models.

关键词： Drug-resistance animal models Hepatitis B virus Hydrodynamic injection

Establishment and validation of standardized animal models of spinal cord injury by normal external force-caused fracture dislocation

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Neural Regeneration Research 2011年第35期6卷 2732-2738页

作者： Weibing Shuang Qiang Liu Shoubin Jiao Yang Yang Department of Urology the First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi Province China Department of Urology the Sixth Agricultural Division Hospital of Xinjiang Production and Construction Corps Wujiaqu 831300 Xinjiang Uygur Autonomous Region China Department of Orthopedics the First Hospital of Shanxi Medical University Taiyuan 030001 Shanxi Province China

The duplication of animal models plays a key role in spinal cord injury research; however, there has been limited study into normal, external force-derived fracture dislocation. This study adopted experimental devices, designed in-house, to construct standardized ventral and dorsal spinal cord injury animal models of 6 g and 17 g falling from a height of 2, 4, and 10 cm, and 15, 30 or 50 g transversal compression on the spinal cord. The results showed that gradual increases in the degree of histopathological injury led to decreased Tarlov and Basso, Beattie and Bresnahan scores for the behavioral test, and increased Ashworth scores for the hind limb. Furthermore, there was a gradual decline in the slope test in the rats with dorsal spinal cord injury that correlated to increases in the falling substance weight or falling height. Similar alterations were observed in the ventral spinal cord injured rats, proportional to the increase in compression weight. Our experimental findings indicate that the standardized experimental rat models of dorsal and ventral spinal cord injury are stable, reliable and reproducible.

关键词： spinal cord injury spinal cord compression animal models external force fracture dislocation behavior histopathology

Magnesium-based materials in orthopaedics:material properties and animal models

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Biomaterials Translational 2021年第3期2卷 197-213页

作者： Xirui Jing Qiuyue Ding Qinxue Wu Weijie Su Keda Yu Yanlin Su Bing Ye Qing Gao Tingfang Sun Xiaodong Guo Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina Department of Clinical Medicine Hubei Enshi CollegeEnshiHubei ProvinceChina

As a new generation of medical metal materials,degradable magnesium-based materials have excellent mechanical properties and osteogenic promoting ability,making them promising materials for the treatment of refractory bone diseases.animal models can be used to understand and evaluate the performance of materials in complex physiological environments,providing relevant data for preclinical evaluation of implants and laying the foundation for subsequent clinical studies.To date,many researchers have studied the biocompatibility,degradability and osteogenesis of magnesium-based materials,but there is a lack of review regarding the effects of magnesium-based materials in vivo.In view of the growing interest in these materials,this review briefly describes the properties of magnesium-based materials and focuses on the safety and efficacy of magnesium-based materials in vivo.Various animal models including rats,rabbits,dogs and pigs are covered to better understand and evaluate the progress and future of magnesium-based materials.This literature analysis reveals that the magnesium-based materials have good biocompatibility and osteogenic activity,thus causing no adverse reaction around the implants in vivo,and that they exhibit a beneficial effect in the process of bone repair.In addition,the degradation rate in vivo can also be improved by means of alloying and coating.These encouraging results show a promising future for the use of magnesium-based materials in musculoskeletal disorders.

关键词： animal models bone regeneration magnesium magnesium alloy tissue engineering