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Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

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Food Science and Human Wellness 2024年第2期13卷 668-680页

作者： Gang Yu Yuhao Jiang Shuifeng Zhang Pengpeng Liu Shunyu Wang Huadong Sheng Yanbo Wang Qiaozhi Zhang Linglin Fu Food Safety Key Laboratory of Zhejiang Province School of Food Science and BiotechnologyZhejiang Gongshang UniversityHangzhou 310018China Zhejiang Fangyuan Test Group Co. Ltd.Hangzhou 310018China Key Laboratory of Biosafety Detection for Zhejiang Market Regulation Hangzhou 310018China Zhejiang Liziyuan Food Co. LtdJinhua 321031China

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.

关键词： Food allergy mouse models Epicutaneous sensitization Th2 response Gut microbiota

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Transgenic dry eye mouse models: powerful tools to study dry eye disease

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International Journal of Ophthalmology(English edition) 2022年第4期15卷 635-645页

作者： Dan-Yi Qin Li-Xiang Wang Ying-Ping Deng Department of Ophthalmology West China Hospital of Sichuan UniversityChengdu 610041Sichuan ProvinceChina

Dry eye disease(DED) is one of the most common chronic multifactorial ocular surface diseases with high prevalence and complex pathogenesis. DED results in several ocular discomforts, vision fluctuation, and even potential damage of the ocular surface, bringing heavy burdens both on individuals and the society. The pathology of DED consists of tear film hyperosmolarity and immune responses on the ocular surface. Mice are widely used for developing models that simulate human DED features for investigating its pathogenesis and treatment. DED can be classified into aqueous-deficiency dry eye(ADDE) and evaporative dry eye(EDE). ADDE can be further divided into Sj?gren syndrome dry eye(SSDE) and non-Sj?gren syndrome dry eye(NSSDE). SSDE mouse models include natural strains, typified by non-obese diabetic(NOD) mice, and genetically engineered ones, like Aire-/-and Id3 knockout mice. Intrinsic EDE mainly refers to meibomian gland dysfunction(MGD). Eda-/-Tabby, Sod1-/-, Elovl1-/-are the most common transgenic MGD mouse models. Transgenic mouse models provide useful tools for studying the pathogenesis of DED and evaluating its novel therapies. This review compares the major transgenic dry eye mouse models and discusses their applications in DED research.

关键词： dry eye disease transgenic mouse models ocular surface pathology

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mouse models in male fertility research

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Asian Journal of Andrology 2011年第1期13卷 139-151页

作者： Duangporn Jamsai Moira K O＇Bryan Department of Anatomy and Developmental Biology The Australian Research Council （ARC） Centre of Excellence in Biotechnology and Development Monash University Melbourne Victoria 3800 Australia

Limited knowledge of the genetic causes of male infertility has resulted in few treatment and targeted therapeutic options. Although the ideal approach to identify infertility causing mutations is to conduct studies in the human population, this approach has progressed slowly due to the limitations described herein. Given the complexity of male fertility, the entire process cannot be modeled in vitro. As such, animal models, in particular mouse models, provide a valuable alternative for gene identification and experimentation. Since the introduction of molecular biology and recent advances in animal model production, there has been a substantial acceleration in the identification and characterization of genes associated with many diseases, including infertility. Three major types of mouse models are commonly used in biomedical research, including knockoutJknockin/gene-trapped, transgenic and chemical-induced point mutant mice. Using these mouse models, over 400 genes essential for male fertility have been revealed. It has, however, been estimated that thousands of genes are involved in the regulation of the complex process of male fertility, as many such genes remain to be characterized. The current review is by no means a comprehensive list of these mouse models, rather it contains examples of how mouse models have advanced our knowledge of post-natal germ cell development and male fertility regulation.

关键词： infertility male fertility mouse models spermatogenesis

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Transgenic mouse models for studying adult neurogenesis

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Frontiers in Biology 2016年第3期11卷 151-167页

作者： Fatih Semerci Mirjana Maletic-Savatic Program in Developmental Biology Baylor College of Medicine Houston TX 77030 USA Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital Houston TX 77030 USA Department of Pediatrics-Neurology Department of Neuroscience and Structural and Computational Biology and Molecular Biophysics Baylor College of Medicine Houston TX 77030 USA

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells （NSCs）, are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associatedcognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has garnered significant interest because targeting it could be a novel potential therapeutic strategy for these disorders. However, if we are to use nenrogenesis to halt or reverse hippocampal-related pathology, we need to understand better the core molecular machinery that governs NSC and their progeny. In this review, we summarize a wide variety of mouse models used in adult neurogenesis field, present their advantages and disadvantages based on specificity and efficiency of labeling of different cell types, and review their contribution to our understanding of the biology and the heterogeneity of different cell types found in adult neurogenic niches.

关键词： adult neurogenesis mouse models neural stem cells neuroprogenitors lineage tracing

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Translating translational research： mouse models of human disease

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Cellular & Molecular Immunology 2013年第5期10卷 373-374页

作者： Amanda M Burkhardt Department of Physiology and Biophysics School of Medicine University of California Irvine Irvine CA USA Institute for Immunology University of California Irvine Irvine CA USA

Translational research has become increasingly popular in recent years.Within the field of medical research, ani- mal models are considered valuable research tools that provide insight into the complex world of human diseases. Inbred animals eliminate several of the challenges of human studies and allow researchers to conduct disease research on, arguably, the most controlled model system possible. The ease with which ani- mal models allow us to advance research often leads us to ignore the possibility that these studies may only provide limited translational potential to humans.

关键词： Translating translational mouse models human disease

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Generation and characterization of Men1 mutant mouse models for studying MEN1 disease

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Journal of Pancreatology 2019年第2期2卷 60-63页

作者： Ya-kun Luo Razan A.Ziki Chang X.Zhang Univ Lyon UniversitéClaude Bernard Lyon 1INSERM 1052CNRS 5286Centre Léon BérardCentre de recherche en cancérologie de LyonLyon F-69008France

Patients with multiple endocrine neoplasia type 1(MEN1)mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages.Following its identification in the late 1990s,laboratories around the world,including our own,used gene-targeting approaches in murine models to study the MEN1 gene and its related diseases.Subsequently,this field of research witnessed an upsurge in the use of Men1 mutant mouse models to dissect MEN1 functions.These studies led to unraveling the natural history of MEN disease,and highlighted cellular and molecular mechanisms underlying the development of the disease.In this review,we present the currently available data concerning the generation and characterization of Men1 mutant mouse models in connection with MEN1 syndrome.

关键词： mouse models The MEN1 gene Tumorigenesis

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Generation and characterization ofmutant mouse models for studying MEN1 disease

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胰腺病学杂志(英文) 2019年第2期02卷 60-61-62-63页

作者： LuoYa-kun ZikiRazanA. ZhangChangX. CNRS5286 CentreLéonBérard CentrederechercheencancérologiedeLyon FranceUnivLyon INSERM1052 UnivLyon UniversitéClaudeBernardLyon1

Patients with multiple endocrine neoplasia type 1 (MEN1) mutations are predisposed to MEN1 syndrome affecting various endocrine cell lineages. Following its identification in the late 1990s, laboratories around the world, including our own, used gene-targeting approaches in murine models to study theMEN1 gene and its related diseases. Subsequently, this field of research witnessed an upsurge in the use ofMen1 mutant mouse models to dissect MEN1 functions. These studies led to unraveling the natural history of MEN disease, and highlighted cellular and molecular mechanisms underlying the development of the disease. In this review, we present the currently available data concerning the generation and characterization ofMen1 mutant mouse models in connection with MEN1 syndrome.

关键词： mouse models TheMEN1 gene Tumorigenesis

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Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

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Science China(Life Sciences) 2022年第12期65卷 2517-2526页

作者： Zhe Chen Linlin Bao Bin Zhu Hua Fu Shuangli Zhu Tianjiao Ji Ying Xue Chuan Liu Xurong Wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo Xu Chuan Qin Hongrong Liu Qi Jin MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Beijing Key Laboratory for Animal models of Emerging and Remerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China School of Computer Science and Engineering Hunan University of Science and TechnologyXiangtan 411201China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua UniversityBeijing 100084China Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityChangsha 410081China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310058China

Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to death.Currently,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are available.Here,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in cells.The cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of VP1.In a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic treatment.In particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.

关键词： enterovirus A71 antibody mouse models cryo-electron microscopy

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CMT1A current gene therapy approaches and promising biomarkers

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Neural Regeneration Research 2023年第7期18卷 1434-1440页

作者： Marina Stavrou Kleopas AKleopa Neuroscience Department The Cyprus Institute of Neurology and GeneticsNicosiaCyprus Center for Neuromuscular Disorders The Cyprus Institute of Neurology and GeneticsNicosiaCyprus

Charcot-Marie-Tooth neuropathies(CMT)constitute a group of common but highly heterogeneous,non-syndromic genetic disorders affecting predominantly the peripheral nervous system.CMT type 1A(CMT1A)is the most frequent type and accounts for almost~50%of all diagnosed CMT cases.CMT1A results from the duplication of the peripheral myelin protein 22(PMP22)gene.Overexpression of PMP22 protein overloads the protein folding apparatus in Schwann cells and activates the unfolded protein response.This leads to Schwann cell apoptosis,dys-and de-myelination and secondary axonal degeneration,ultimately causing neurological disabilities.During the last decades,several different gene therapies have been developed to treat CMT1A.Almost all of them remain at the pre-clinical stage using CMT1A animal models overexpressing PMP22.The therapeutic goal is to achieve gene silencing,directly or indirectly,thereby reversing the CMT1A genetic mechanism allowing the recovery of myelination and prevention of axonal loss.As promising treatments are rapidly emerging,treatment-responsive and clinically relevant biomarkers are becoming necessary.These biomarkers and sensitive clinical evaluation tools will facilitate the design and successful completion of future clinical trials for CMT1A.

关键词： axonal degeneration biomarkers Charcot-Marie-Tooth disease gene therapy inherited neuropathy mouse models

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A new age in understanding adult hippocampal neurogenesis in Alzheimer’s disease

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Neural Regeneration Research 2022年第12期17卷 2615-2618页

作者： Maya A.Hanspal Sébastien Gillotin MRL London Discovery MSDLondon Bioscience Innovation CentreLondonUK

Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.

关键词： adult hippocampal neurogenesis Alzheimer’s disease cognition human tissue induced pluripotent stem cell mouse models neurodegeneration therapeutics tractable target

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