Alb-cre/DTR小鼠可诱导性肝损伤模型的建立

目的建立Alb-cre/DTR双转基因小鼠模型并进行相关表型分析,在此基础上建立可诱导性肝损模型,用于肝脏疾病的相关研究。方法将引进的Alb-cre和DTR小鼠扩繁后,通过杂交的方式获得双转基因小鼠。提取小鼠尾部组织DNA,利用PCR方法进行基因型鉴定。在双转基因小鼠上腹腔注射白喉毒素,之后在不同时间点进行称重、采血,检测血清ALT、AST水平。结果将Alb-cre和DTR小鼠杂交、筛选后获得了Alb-cre/DTR双转基因小鼠,对该小鼠使用0.625 ng/g剂量的白喉毒素,可使小鼠血清中ALT与AST水平显著升高,解剖小鼠后观察到肝整体变白,HE染色结果显示肝细胞明显坏死。结论成功建立可诱导特异性肝损伤小鼠模型。     

用于肝脏疾病研究的人源化小鼠模型概述

肝脏疾病是危害人类健康的重要疾病之一,合适的小动物模型的缺乏在很大程度上制约了肝脏疾病的相关研究。人源化小鼠作为重要动物模型之一,在肝脏疾病的研究中有巨大的应用价值。本文对早期的uPA小鼠、FAH小鼠、TK-NOG小鼠和近年来的AFC8小鼠等几种应用较为广泛且有代表性的人源化小鼠模型及其在肝脏疾病研究中的应用进行了对比分析,阐述了它们各自的模型原理和优缺点,以期对人源化小鼠应用于人类肝脏疾病的研究具有较为直观的认识。     

miR-5572转基因小鼠构建病态窦房结综合征疾病模型的繁殖与鉴定

目的探讨miR-5572转基因小鼠构建病态窦房结综合征疾病模型的可行性。方法繁殖与鉴定了miR-5572 F1及F2代野生型纯合子及杂合子小鼠,并通过形态学、心电图记录及窦房结组织Cav1.2、Cav1.3mRNA和蛋白表达水平测定来观察疾病模型。结果 F2代miR-5572纯合子敲入小鼠在形态上较野生型小鼠生长缓慢,体型较小。相较于杂合子和野生型小鼠,纯合小鼠的平均心率明显偏低(P0.05),差异有显著性。miR-5572纯合子小鼠窦房结组织Cav1.2、Cav1.3 mRNA和蛋白表达水平低于野生型(P0.05),差异有显著性。结论过表达miR-5572转基因小鼠可以构建病态窦房结综合征疾病模型。     

HSF1基因敲除小鼠心脏老化淀粉样变模型建立与检测

目的探讨小鼠心脏淀粉样变疾病模型的建立以及淀粉样纤维在小鼠心脏组织中的形态学观察。方法采用雌性热休克转录因子1(heat shock factor 1,HSF1)基因敲除(Hsf1~(-/-))小鼠和野生型ICR小鼠进行淀粉样变诱导实验,构建老化淀粉样变疾病模型。模型构建2个月后,通过刚果红染色、免疫组织化学、电镜等方法对各个实验组心脏组织中淀粉样变沉积情况及心功能进行评估。结果通过淀粉样变诱导实验2个月后,Hsf1~(-/-)小鼠与野生型小鼠各组织中均有淀粉样物质沉积,但心脏组织中淀粉样纤维沉积程度显著不同,且沉积部位主要位于小鼠心肌中的结缔组织内及小血管的管壁,并引起心肌细胞损伤。此外,Hsf1~(-/-)小鼠心脏淀粉样变程度显著高于野生型小鼠,心功能损伤程度显著高于野生型小鼠。结论 Hsf1基因敲除小鼠可用于构建心脏淀粉样变疾病的动物模型,并应用于心脏淀粉样变疾病的基础及临床研究。     

小鼠脐血移植模型研究进展

脐血中含有丰富的原始造血干细胞,由于免疫细胞发育不成熟,抗原表达和功能活性低下,移植物抗宿主疾病发生率低。脐血来源丰富、不易受病毒及残留肿瘤细胞的污染,越来越多地作为造血干细胞的优质来源在临床上广泛应用。通过建立小鼠脐血移植模型,对临床多种疾病尤其是对恶性血液病的造血干细胞移植研究提供有效途径,可以对脐血的生物学功能、植入过程、移植疗效做进一步研究,不断优化的小鼠移植模型对我们解读人类疾病的发病机理、疾病进程起到推动作用,本文将从小鼠种属的选择、移植模型的构建及脐血移植模型新进展等方面对进行综述。     

线粒体疾病小鼠模型的建立及病理生理学研究

线粒体疾病是机体ATP合成障碍、供能不足引起的多系统疾病。近十年来,随着线粒体疾病小鼠模型的不断建立和完善,发现核DNA（nuclear DNA,nDNA）或（和）线粒体DNA（mitochondrial DNA,mtDNA）突变造成线粒体氧化磷酸化功能缺陷是其发病的主要原因。将着重介绍线粒体氧化磷酸化功能缺陷导致线粒体疾病的小鼠模型的建立及其病理生理学特点。     

空肠弯曲杆菌感染小鼠模型的研究进展

空肠弯曲杆菌主要导致食源性胃肠疾病,对人类健康有重要影响,然而相关小鼠感染模型的建立是该致病菌研究的难点.本文综述了影响空肠弯曲杆菌感染模型建立的关键因素,包括菌株的毒力因子、小鼠的品系、免疫功能、肠道菌群、饮食组成、宿主适应等因素,以期为成功建立合适的小鼠感染模型提供参考.     

小鼠模型在铁代谢研究中的应用

铁代谢在维持生命活动中至关重要,机体铁代谢紊乱会导致贫血和人类遗传性血色病等诸多疾病,对人体健康造成危害。在铁代谢研究领域,小鼠模型具有人群及细胞模型所不具备的优势,可以最准确的表现相应基因及通路在铁代谢调控中的生理作用。利用基因敲除及转基因小鼠模型,许多铁代谢相关的基因及调控通路被发现,有助于深入了解铁稳态调控的分子机制。这些小鼠模型为治疗铁代谢紊乱相关疾病潜在药物的开发和评估提供了理想的平台。     

H9N2亚型猪流感病毒感染BALB/c小鼠动物模型的建立

目的建立H9N2亚型猪流感病毒感染BALB/c小鼠动物模型,为研究病毒致病机制提供模型动物。方法通过滴鼻的方法将H9N2亚型猪流感病毒感染BALB/c小鼠,观察小鼠的症状和组织病理变化。结果 BALB/c小鼠的临床症状明显,病理变化典型。结论 H9N2亚型猪流感病毒感染BALB/c小鼠的疾病模型成功建立。     

封面说明

正小鼠是最广泛使用的模式生物,构建基因改造的小鼠模型是研究基因功能和疾病发生机制的重要手段。近年来随着CRISPR/Cas9基因编辑技术的发现,加速了整个基因改造领域的发展,小鼠资源库的全球格局也在发生变化,呈现出小鼠模型标准化、精准化、供应规模化的特点。如何利用我国科学家自主研发的全新小鼠基因改造技术——"人造精子细胞"介导的半克隆技术,来摆脱我国小鼠实验动物"卡脖子"风险,     

Mouse Models of Polyglutamine Diseases in Therapeutic Approaches: Review and Data Table. Part II

Mouse models of human diseases are created both to understand the pathogenesis of the disorders and to find successful therapies for them. This work is the second part in a series of reviews of mouse models of polyglutamine (polyQ) hereditary disorders and focuses on in vivo experimental therapeutic approaches. Like part I of the polyQ mouse model review, this work is supplemented with a table that contains data from experimental studies of therapeutic approaches in polyQ mouse models. The aim of this review was to characterize the benefits and outcomes of various therapeutic strategies in mouse models. We examine whether the therapeutic strategies are specific to a single disease or are applicable to more than one polyQ disorder in mouse models. In addition, we discuss the suitability of mouse models in therapeutic approaches. Although the majority of therapeutic studies were performed in mouse models of Huntington disease, similar strategies were also used in other disease models.     

Attempts to understand the mechanisms of mitochondrial diseases: The reverse genetics of mouse models for mitochondrial disease

BackgroundMitochondrial disease is a general term for a disease caused by a decline in mitochondrial function. The pathology of this disease is extremely diverse and complex, and the mechanism of its pathogenesis is still unknown. Using mouse models that develop the disease via the same processes as in humans is the easiest path to understanding the underlying mechanism. However, creating a mouse model is extremely difficult due to the lack of technologies that enable editing of mitochondrial DNA (mtDNA).Scope of reviewThis paper outlines the complex pathogenesis of mitochondrial disease, and the difficulties in producing relevant mouse models. Then, the paper provides a detailed discussion on several mice created with mutations in mtDNA. The paper also introduces the pathology of mouse models with mutations including knockouts of nuclear genes that directly affect mitochondrial function.Major conclusionsSeveral mice with mtDNA mutations and those with nuclear DNA mutations have been established. Although these models help elucidate the pathological mechanism of mitochondrial disease, they lack sufficient diversity to enable a complete understanding. Considering the variety of factors that affect the cause and mechanism of mitochondrial disease, it is necessary to account for this background diversity in mouse models as well.General significanceMouse models are indispensable for understanding the pathological mechanism of mitochondrial disease, as well as for searching new treatments. There is a need for the creation and examination of mouse models with more diverse mutations and altered nuclear backgrounds and breeding environments.     

Transgenic mouse models of Alzheimer's disease

Recent advances in the understanding of the genetic basis of Alzheimer's disease have enabled the production of transgenic mouse models of the disease. Utilizing both cDNA- and genomic-based approaches, these mouse models for Alzheimer's disease have already provided valuable insights into the pathogenesis of the disease and potential therapeutic interventions.     

Proteome analysis of mouse model systems: A tool to model human disease and for the investigation of tissue-specific biology

The molecular dissections of the mechanistic pathways involved in human disease have always relied on the use of model organisms. Among the higher mammalian organisms, the laboratory mouse (Mus musculus) is the most widely used model. A large number of commercially-available, inbred strains are available to the community, including an ever growing collection of transgenic, knock-out, and disease models. Coupled to availability is the fact that animal colonies can be kept under standardized housing condition at most major universities and research institutes, with relative ease and cost efficiency (compared to larger vertebrates). As such, mouse models to study human biology and disease remains extremely attractive. In the current review we will provide an historic overview of the use of mouse models in proteome research with a focus on general tissue and organelle biology, comparative proteomics of human and mouse and the use of mouse models to study cardiac disease.     

Inflammation in transgenic mouse models of neurodegenerative disorders

Much evidence is available that inflammation contributes to the development of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Our review investigates how well current mouse models reflect this aspect of the pathogenesis.Transgenic models of AD have been available for several years and are the most extensively studied. Modulation of cytokine levels, activation of microglia and, to a lesser extent, activation of the complement system have been reported. Mouse models of PD and HD so far show less evidence for the involvement of inflammation.An increasing number of transgenic mouse strains is being created to model human neurodegenerative diseases. A perfect model should reflect all aspects of a disease. It is important to evaluate continuously the models for their match with the human disease and reevaluate them in light of new findings in human patients.Although none of the transgenic mouse models recapitulates all aspects of the human disorder they represent, all models have provided valuable information on basic molecular pathways. In particular, the mouse models of Alzheimer disease have also led to the development of new therapeutic strategies such as vaccination and modulation of microglial activity.     

小鼠过敏性哮喘模型的研究进展及评价

支气管哮喘（简称哮喘）是常见的慢性病,随着过敏患者的增加,小鼠过敏性哮喘模型的研究越来越重要。本文通过对近年来国内外小鼠过敏性哮喘的实验研究文献进行总结,从实验小鼠的选择、制备模型的方法及模型的评价指标等方面进行综合分析,为进一步开展哮喘研究提供帮助。     

Protein farnesyltransferase inhibitors and progeria

Genetic mutations that lead to an accumulation of farnesyl-prelamin A cause progeroid syndromes, including Hutchinson-Gilford progeria syndrome. It seemed possible that the farnesylated form of prelamin A might be toxic to mammalian cells, accounting for all the disease phenotypes that are characteristic of progeria. This concept led to the hypothesis that protein farnesyltransferase inhibitors (FTIs) might ameliorate the disease phenotypes of progeria in mouse models. Thus far, two different mouse models of progeria have been examined. In both models, FTIs improved progeria-like disease phenotypes. Here, prelamin A post-translational processing is discussed and several mutations underlying human progeroid syndromes are described. In addition, recent data showing that FTIs ameliorate disease phenotypes in a pair of mouse models of progeria are discussed.     

A functional analysis of mouse models of cardiac disease through metabolic profiling

Since the completion of the human and mouse genomes, the focus in mammalian biology has been on assessing gene function. Tools are needed for assessing the phenotypes of the many mouse models that are now being generated, where genes have been "knocked out," "knocked in," or mutated, so that gene expression can be understood in its biological context. Metabolic profiling of cardiac tissue through high resolution NMR spectroscopy in conjunction with multivariate statistics has been used to classify mouse models of cardiac disease. The data sets included metabolic profiles from mouse models of Duchenne muscular dystrophy, two models of cardiac arrhythmia, and one of cardiac hypertrophy. The metabolic profiles demonstrate that the strain background is an important component of the global metabolic phenotype of a mouse, providing insight into how a given gene deletion may result in very different responses in diverse populations. Despite these differences associated with strain, multivariate statistics were capable of separating each mouse model from its control strain, demonstrating that metabolic profiles could be generated for each disease. Thus, this approach is a rapid method of phenotyping mouse models of disease.