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Characteristics of gut microbiota in representative mice strains:Implications for biological research

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Animal Models and Experimental medicine 2022年第4期5卷 337-349,I0002页

作者： Jianguo Guo Chenchen Song Yunbo Liu Xuying Wu Wei Dong Hua Zhu Zhiguang Xiang Chuan Qin Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Background:Experimental animals are used to study physiological phenomena,pathological mechanisms,and disease prevention.The gut microbiome is known as a potential confounding factor for inconsistent data from preclinical studies.Although many gut microbiome studies have been conducted in recent decades,few have focused on gut microbiota fluctuation among representative mouse strains.Methods:A range of frequently used mouse strains were selected from 34 isolation packages representing disease-related animal(DRA),immunity defect animal(IDA),or gene-editing animal(GEA)from the BALB/c and C57BL/6J backgrounds together with normal mice,and their microbial genomic DNA were isolated from mouse feces to sequence for the exploration of gut microbiota.Results:Mouse background strain,classification,introduced source,introduced year,and reproduction type significantly affected the gut microbiota structure(p<0.001 for all parameters),with background strain contributing the greatest influence(R^(2)=0.237).In normal groups,distinct gut microbiota types existed in different mouse strains.Sixty-four core operational taxonomic units were obtained from normal mice,and 12 belonged to Lactobacillus.Interestingly,the gut microbiota in C57BL/6J was more stable than that in BALB/c mice.Furthermore,the gut microbiota in the IDA,GEA,and DRA groups significantly differed from that in normal groups(p<0.001 for all).Compared with the normal group,there was a significantly higher Chao 1 and Shannon index(p<0.001 for all)in the IDA,GEA,and DRA groups.Markedly changed classes occurred with Firmicutes and Bacteroidetes.The abundances of Helicobacter,Blautia,Enterobacter,Bacillus,Clostridioides,Paenibacillus,and Clostridiales all significantly decreased in the IDA,GEA,and DRA groups,whereas those of Saccharimonas,Rikenella,and Odoribacter all significantly increased.

关键词： Bacteroidetes BALB/c mice C57BL/6J disease-related animal Firmicutes gene-editing animal gut microbiota i mmunity defect animal strains

Autophagy and autophagy-related molecules in neurodegenerative diseases

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Animal Models and Experimental medicine 2023年第1期6卷 10-17页

作者： Changsong Dou Yu Zhang Ling Zhang Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Key Laboratory of Human Diseases Animal ModelInstitute of Laboratory Animal SciencesComparative Medicine CenterPeking Union Medical College(PUMC)Chinese Academy of Medical Sciences(CAMS)BeijingChina Beijing Engineering Research Center for Experimental Animal Models of human Critical diseases Beijing Comparative Medicine CenterPeking Union Medical College(PUMC)Chinese Academy of Medical Sciences(CAMS)BeijingChina

Autophagy is one of the degradation pathways to remove proteins or damaged or-ganelles in cells that plays an important role in neuroprotection.Different stages of autophagy are regulated by autophagy-related genes,and many molecules such as transcription factor EB(TFEB)are involved.The complete autophagy process plays an important role in maintaining the dynamic balance of autophagy and is crucial to the homeostasis of intracellular substance and energy metabolism.Autophagy balance is disrupted in neurodegenerative diseases,accounting for a variety of degeneration dis-orders.These impairments can be alleviated or treated by the regulation of autophagy through molecules such as TFEB.

关键词： autophagy mitophagy neurodegenerative TFEB

Era of the 4D animal model

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Animal Models and Experimental medicine 2023年第2期6卷 178-182页

作者： Lihong Zhang Jindan Guo Jiangning Liu NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

关键词： animal model database digitally display human diseases spatiotemporal landscapes

Characteristics of animal models for COVID-19

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Animal Models and Experimental medicine 2022年第5期5卷 401-409页

作者： Feifei Qi Chuan Qin Beijing key laboratory for Animal Models of Emerging and Reemerging Infectious diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina National Center of Technology Innovation for Animal Model BeijingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is the causative agent of coronavirus disease 2019(COVID-19),the most consequential pandemic of this century,threatening human health and public safety.SARS-CoV-2 has been continuously evolving through mutation of its genome and variants of concern have emerged.The World Health Organization R&D Blueprint plan convened a range of expert groups to develop animal models for COVID-19,a core requirement for the prevention and control of SARS-CoV-2 pandemic.The animal model construction techniques developed during the SARS-CoV and MERS-CoV pandemics were rapidly deployed and applied in the establishment of COVID-19 animal models.To date,a large number of animal models for COVID-19,including mice,hamsters,minks and nonhuman primates,have been established.Infectious diseases produce unique mani-festations according to the characteristics of the pathogen and modes of infection.Here we classified animal model resources around the infection route of SARS-CoV-2,and summarized the characteristics of the animal models constructed via transnasal,localized,and simulated transmission routes of infection.

关键词： animal model characteristics establishment SARS-CoV-2

Sequentially immune-induced antibodies could cross-neutralize SARS-CoV-2 variants

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Animal Models and Experimental medicine 2022年第1期5卷 89-93页

作者： Qi Lv Shasha Zhou Feifei Qi Yaqing Zhang Fengdi Li Mingya Liu Linlin Bao Beijing key laboratory for Animal Models of Emerging and Reemerging Infectious diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina National Center of Technology Innovation for Animal Model BeijingChina

Background:The Omicron(B.1.1.529)SARS-COV-2 variant has raised serious concerns because of its unprecedented rapid rate of spreading and the fact that there are 36 mutations in the spike protein.Since the vaccine-induced neutralizing antibody targets are the spike protein,this may lead to the possibility of vaccine-induced hu-moral immunity escape.Methods:We measured the neutralizing activity in vitro for Omicron and compared this with wild type(WH-09)and Delta variants in human and monkey sera from different types of immunity.The monkey sera samples were collected at 1 and 3 months post three-dose inactivated(PiCoVacc)and recombinant protein(ZF2001)vaccination.human sera were collected from 1 month post three-dose inactivated vaccination.Results:In inactivated vaccine sera,at 1/3 months post three-dose,geometric mean titers(GMTs)of neutralization antibody(NAb)against the Omicron variant were 4.9/5.2-fold lower than those of the wild type.In recombinant protein vaccine sera,GMTs of NAb against Omicron were 15.7/8.9-fold lower than those of the wild type.In human sera,at 1 month post three-dose inactivated vaccination,GMTs of NAb against Omicron were 3.1-fold lower than those of the wild type.Conclusion:This study demonstrated that despite a reduction in neutralization titers,cross-neutralizing activity against Omicron and Delta variants was still observed after three doses of inactivated and recombinant protein vaccination.

关键词： cross-neutralize Omicron SARS-CoV-2 sequentially immune

Overexpression of ACE2 ameliorates Aβ-induced blood–brain barrier damage and angiogenesis by inhibiting NF-κB/VEGF/VEGFR2 pathway

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Animal Models and Experimental medicine 2023年第3期6卷 237-244页

作者： Xueling Zhang Yu Zhang Ling Zhang Chuan Qin Institute of laboratory Animal Sciences CAMS&PUMCBeijingChina National human diseases Animal Model Resource Center BeijingChina NHC Key Laboratory of Human Disease Comparative Medicine BeijingChina Changping National laboratory(CPNL) BeijingChina

Background:Pathological angiogenesis and blood–brain barrier damage may play an important role in Alzheimer's disease(AD).ACE2 is mainly expressed on the surface of endothelial cells in brain.Recent studies have shown that the expression of ACE2 in AD is reduced,but its role in AD is still unclear.Method:We induced AD damage in endothelial cells using Aβ25-35 and overexpressed ACE2 in bEend.3 cells through lentiviral transfection.We detected the effect of Aβ25-35 on cell viability using the CCK-8 assay and examined the effect of overexpressing ACE2 on angiogenesis using an angiogenesis assay.We used western blot and cell immunofluorescence to detect changes in the expression of the VEGF/VEGFR2 pathway,tight junction protein,and NF-κB pathway.Results:Aβ25-35 treatment significantly decreased the expression of ACE2 and reduced cell viability.ACE2 overexpression(1)reduced the number of branches and junctions in tube formation,(2)inhibited the activation of the VEGF/VEGFR2 pathway induced by Aβ25-35,(3)increased the expression of TJPs,including ZO-1 and claudin-5,and(4)restored Aβ25-35-induced activation of the NF-κB pathway.Conclusion:Overexpression of ACE2 can improve pathological angiogenesis and blood–brain barrier damage in AD models in vitro by inhibiting NF-κB/VEGF/VEGFR2 pathway activity.ACE2 may therefore represent a therapeutic target for endothelial cell dysfunction in AD.

关键词： ACE2 Alzheimer's disease angiogenesis blood-brain barrier VEGF

Effectiveness and mechanisms of adiposederived stem cell therapy in animal models of Parkinson’s disease:a systematic review and meta-analysis

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Translational Neurodegeneration 2021年第2期10卷 166-177页

作者： keya Li Xinyue Li Guiying Shi Xuepei Lei Yiying Huang Lin Bai Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China

Animal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells(ADSCs).Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease(PD).Here,eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention.Quality assessment was conducted using a 10-item risk of bias tool.For the subsequent meta-analysis,study characteristics were extracted and effect sizes were computed.Ten out of 2324 published articles(n=169 animals)were selected for further meta-analysis.After ADSC therapy,the rotation behavior(10 experiments,n=156 animals)and rotarod performance(3 experiments,n=54 animals)were improved(P<0.00001 and P=0.0003,respectively).The rotation behavior test reflected functional recovery,which may be due to the neurogenesis from neuronally differentiated ADSCs,resulting in a higher pooled effect size of standard mean difference(SMD)(−2.59;95%CI,−3.57 to−1.61)when compared to that of primitive cells(−2.18;95%CI,−3.29 to−1.07).Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect.Following the transplantation of ADSCs,tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36[6.85,19.86].Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD.The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects.The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.

关键词： Parkinson’s disease Adipose-derived stem cells Animal model Stem cell therapy Meta-analysis Neurogenesis Neuroprotection

Microarray microRNA profiling of urinary exosomes in a 5XFAD mouse model of Alzheimer’s disease

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Animal Models and Experimental medicine 2021年第3期4卷 233-242页

作者： Zhiqi Song Yajin Qu Yanfeng Xu Ling Zhang Li Zhou Yunlin Han Wenjie Zhao Pin Yu Yu Zhang Xianglei Li Chuan Qin Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of HealthBeijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Background:Alzheimer's disease(AD)is an incurable and irreversible neurodegen-erative disease,without a clear pathogenesis.Therefore,identification of candidates before amyloid-βplaque(Aβ)deposition proceeds is of major significance for earlier intervention in AD.Methods:To explore the potential noninvasive earlier biomarkers of AD in a 5XFAD mouse model,microRNAs(miRNAs)from urinary exosomes in 1-month-old pre-Aβaccumulation 5XFAD mice models and their littermate controls were profiled by mi-croarray analysis.The differentially expressed miRNAs were further analyzed via droplet digital PCR(ddPCR).Results:Microarray analysis demonstrated that 48 differentially expressed miRNAs(18 upregulated and 30 downregulated),of which six miRNAs-miR-196b-5p,miR-339-3p,miR-34a-5p,miR-376b-3p,miR-677-5p,and miR-721-were predicted to display gene targets and important signaling pathways closely associated with AD pathogenesis and verified by ddPCR.Conclusions:Urinary exosomal miRNAs showing differences in expression prior to Aβ-plaque deposition were identified.These exosomal miRNAs represent potential noninvasive biomarkers that may be used to prevent AD in clinical applications.

关键词： 5XFAD mouse model Alzheimer's disease biomarkers microarray miRNA urinary exosome

Is China ready for monkeypox?

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Animal Models and Experimental medicine 2022年第4期5卷 397-398页

作者： Qiang Wei Institute of laboratory Animal Sciences Chinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of human Critical diseases

Monkeypox is a rare viral infection caused by the monkeypox virus,which is similar to human smallpox.It is also a zoonosis which is found mainly in tropical rain forests of central and western Africa.The monkeypox virus was first detected in grivet at a laboratory in Copenhagen,Denmark,in 1958,and was later found in many African rodents,such as murine and squirrels.Therefore,it is believed that the primary way of infection is through direct human contact with these infected animals.In May 2003,human monkeypox appeared in the Western Hemisphere in the United States and spreaded rapidly,which immediately attracted the attention of all countries.

关键词： infection monkey Africa