Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene functions.The field of genome modification in rabbits has progressed slowly.However,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic pathologies.These models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to mice.This review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.

Finding biomarkers of experience in animals

At a time when there is a growing public interest in animal welfare,it is critical to have objective means to assess the way that an animal experiences a situation.Objectivity is critical to ensure appropriate animal welfare outcomes.Existing behavioural,physiological,and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes.But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal,from negative to positive.In this review,we draw from the knowledge of human biomedical science to propose a list of candidate biological markers(biomarkers)that should reflect the experiential state of non-human animals.The proposed biomarkers can be classified on their main function as endocrine,oxidative stress,non-coding molecular,and thermobiological markers.We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.

Advances in viral encephalitis:Viral transmission,host immunity,and experimental animal models

Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.

Mesenchymal stem cells in the treatment of inflammatory and autoimmune diseases in experimental animal models

Multipotent mesenchymal stromal cells [also known as mesenchymal stem cells(MSCs)] are currently being studied as a cell-based treatment for inflammatory disorders. Experimental animal models of human immune-mediated diseases have been instrumental in establishing their immunosuppressive properties. In this review, we summarize recent studies examining the effectiveness of MSCs as immunotherapy in several widely-studied animal models, including type 1 diabetes, experimental autoimmune arthritis, experimental autoimmune encephalomyelitis, inflammatory bowel disease, graft-vs-host disease, and systemic lupus erythematosus. In addition, we discuss mechanisms identified by which MSCs mediate immune suppression in specific disease models, and potential sources of functional variability of MSCs between studies.

Standardization of experimental animals temporal bone sections

Preparation of the temporal bone for light microscopy is an important step in histological studies of the inner ear. Due to the complexity of structures of the inner ear, it is difficult to measure or compare structures of interest without a commonly accepted standardized measure of temporal bone sections. Therefore, standardization of temporal bone sections is very important for histological assessment of sensory hair cells and peripheral ganglion neurons in the cochlear and vestibular systems. The standardized temporal bone sectioning is oriented to a plane parallel to the outer and internal auditory canals. Sections are collected from the epitympanum to the hypotympanum to reveal layers in the order of the crista ampullaris of the superior and lateral semicircular canals, macula utriculi and macula sacculi, superior vestibular ganglion neurons, macula of saccule and inferior vestibular ganglion neurons, cochlear modiolus, endolymphatic duct and endolymphatic sac, and finally the crista ampullaris of the posterior semicircular canal. Moreover, technical details of preparing for temporal bone sectioning including fixation, decalcification, whole temporal bone staining, embedding penetration, and embedding orientation are also discussed.

Animal experimental studies using small intestine endoscope

AIM To assess the feasibility and safety of a novel enteroscope,negative-pressure suction endoscope in examining the small intestine of a porcine model.METHODS In vitro experiments in small intestinal loops from 20pigs and in vivo experiments in 20 living pigs were conducted.RESULTS In in vitro experiments,a negative pressure of>0.06MPa was necessary for optimal visualization of the intestine,and this pressure did not cause gross or histological damage to the mucosa.For satisfactory examination of the small intestine in vivo,higher negative pressure(>1.00 MPa)was required.Despite this higher pressure,the small intestine did not show any gross or microscopic damage in the suctioned areas.The average time of examination in the living animals was 60±7.67 min.The animals did not experience any apparent ill effects from the procedure.CONCLUSION Small intestine endoscope was safely performed within a reasonable time period and enabled complete visualization of the intestine in most cases.

EVALUATION OF CIRRHOTIC LIVER WITH PERFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING:A PRELIMINARY EXPERIMENTAL STUDY IN ANIMAL MODELS WITH HALF-LIVER CIRRHOSIS

Objective To investigate the role of peffusion-weighted magnetic resonance imaging （MRI） in evaluation of cirrhotic fiver. Methods With a 4F catheter, 1% diluted carbon tetrachloride （ 1 ml/kg） was selectively injected into fight or left hepatic artery of 12 dogs fortnightly. The half fiver into which carbon tetrachloride was injected was called as study side （SS）, while the other half fiver without carbon tetrachloride injection was called as study control side （SCS）. Conventional and peffusion-weighted MRI were performed in every 4 weeks. Via a 4F catheter, 5ml gadolinium diethylentriamine pentaaceti acid （Gd-DTPA） dilution was injected into superior mesenteric artery at the 5th scan. The signal intensity-thne curves of SS, SCS, and portal vein were completed in MR workstation. The maximal relative signal increase （ MRSI）, peak time （ tp）, and slope of the curves were measured. Results On conventional MR images, no abnormalities of externality and signal intensity were observed in both SS and SCS of fiver at each stage. The mean tp, MP, SI, and slope of intensity-time curves in normal fiver were 10. 56 seconds, 1.01, and 10. 23 arbitrary unit （au）/s, respectively. Three parameters of curves didn＇t show obvious change in SCS of fiver at every stage. Abnormal perfusion curves occurred in SS of fiver at the 12th week after the 1st injection. The abnormality of perfusion curve in SS was more and more serious as the times of injection increased. The mean tp, IVlRSI, and slope intensity-time curves in SS of fiver were 19.45 seconds, 0. 43, and 3. 60 au/s respectively at the 24th week. Conclusion Perfusion-weighted imaging can potentially provide information about portal peffusion of hepatic parenchyma, and to some degree, reflect the severity of cirrhosis.

Experimental Study of the Antitumor Activity of Polymetalacrylates against Animal Transplantable Tumors

The antitumor activity of the fourteen polymetalacrylates against two models of murine solid tumors (Lewis lung carcinoma and Acatol adenocarcinoma) as well as the acute toxicity of these compounds has been studied. It was shown that polyacrylates of noble metals (argent, aurum, platinum), namely argacryl (М = Ag), auracryl (М = Au) and platacryl (М = Pt) were the most effective agents among tested compounds against studied tumors. Thus, the tumor growth inhibitory effect of argacryl against Lewis lung carcinoma was equal to 90%, the life-span of treated by this compound animals has increased on 50% in comparison with control. Auracryl induced the inhibition of the Lewis lung carcinoma and Acatol adenocarcinoma development on 60 and 65%, correspondingly and the increasing of the mean life-span of animals with Lewis lung carcinoma on 20% in comparison with control. Platacryl inhibited the growth of Lewis lung carcinoma on 40% increasing the mean life-span of animals on 25% in comparison with control. In this way it was established that argacryl is the agent with the strongest antitumor activity among studied polymetalacrylates. On the basis of obtained data it seems possible to consider polymetalacrylates as a group of agents with the potential antitumor activity suitable for the further deep experimental investigation.

Experimental animal models of pulmonary hypertension:Development and challenges

Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.

Clinical application of full automatic animal experimental cabin of normobaric/hypobaric hypoxia and high carbon dioxide

To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.

Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

Congratulations to the new journal: Animal Models andExperimental Medicine

I would like to extend my best congratulations to all concerned for the publication of the inaugural issue of Animal Models and Experimental Medicine (AMEM), an English journal published jointly by the Chinese Association for Laboratory Animal Sciences (CALAS) and the Institute of Laboratory Animal Sciences of Chinese Academy of Medical Sciences & Peking Union Medical College. Basic medical research has been at the forefront of science and technology development. Essential to that, laboratory animal science is of foundamental importance in biomedical research, providing key advantages in understanding mechanisms of health and disease without posting actual risks to human beings.

Neuroprotective Effects of Sodium Ferulate and Its Antidepressant-Like Effect Measured by Acute and Chronic Experimental Methods in Animal Models of Depression

Antidepressants with novel targets and without side effects are in great demand. Ferulic acid (FA) is a ubiquitous phenolic acid of low toxicity, and sodium ferulate (SF) is its sodium salt. Our previous studies have revealed that FA and SF show significant protective effect on excitotoxicity, we now test its potential neuroprotective and antidepressant-like effects. MTT assay and morphological analysis by fluorescence microscopy were adopted to measure the neuroprotective effects of SF;forced-swimming, tail-suspension, and chronic mild stress (CMS) tests were performed to assess its antidepressant-like activity. The results showed that SF had protection against H2O2-induced oxidative damage and dexamethasone (DXM)-induced neurotoxicity pheochromocytoma (PC12) cells. Acute administration of SF markedly decreased the duration of immobility during forced-swimming in rats and mice and tail-supension tests in mice. However, SF has no any effects on reserpine-induced hypothermia, 5-hydroxytryptophan-induced head-twitch response, and potentiation of noradrenaline toxicity in mice. Chronic administration of SF reversed the effects of CMS on consumption of food and sucrose solution, weight gain, and histopathology of hippocampus by light microscopy, and potently shortened the immobility time during forced-swimming test following CMS in rats. This study provides evidence that SF possesses obviously antidepressant-like activity, and the antidepressant-like effect may result from its neuroprotective effects.

Announcing the launch of a new journal: Animal Models andExperimental Medicine

In the Chinese Year of the Dog,we are pleased to present to you the first issue of the new journal we have organized:Animal Models and Experimental Medicine(AMEM).Why do we need a new journal in this area?Laboratory animal sciences is an emerging interdisciplinary subject,which integrates theories and methods from many disciplines,including biology,medicine,pharmacy,veterinary,bioengineering,biomedical engineering,etc.In recent years,many outstanding papers based on laboratory animals have been published around the world,highlighting how laboratory animal sciences has,among other things,provided systematic biological materials and pertinent technologies for the development of related disciplines;integration into many frontier disciplines;development of new disciplines such as comparative medicine,experimental animal medicine,and comparative biology;and supported development in fields such as life sciences,medicine,food,environment and aerospace.However,there are very few specialized journals in this field,and their impact is very limited.Therefore,it is urgent to establish a professional English-language journal to meet the need of all researchers in this important field.

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

The distribution of the immune system throughout the body complicates in vitro assessments of coronavirus disease 2019(COVID-19)immunobiology,often resulting in a lack of reproducibility when extrapolated to the whole organism.Consequently,developing animal models is imperative for a comprehensive understanding of the pathology and immunology of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.This review summarizes current progress related to COVID-19 animal models,including non-human primates(NHPs),mice,and hamsters,with a focus on their roles in exploring the mechanisms of immunopathology,immune protection,and long-term effects of SARS-CoV-2 infection,as well as their application in immunoprevention and immunotherapy of SARS-CoV-2 infection.Differences among these animal models and their specific applications are also highlighted,as no single model can fully encapsulate all aspects of COVID-19.To effectively address the challenges posed by COVID-19,it is essential to select appropriate animal models that can accurately replicate both fatal and non-fatal infections with varying courses and severities.Optimizing animal model libraries and associated research tools is key to resolving the global COVID-19 pandemic,serving as a robust resource for future emerging infectious diseases.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Focus on cutting-edge research to improve the influence of Animal Models and Experimental Medicine

The year 2022 marks the fifth year of the publication of Animal Models and Experimental Medicine( AMEM). We are intensely proud of the publication of each paper, because we recognize that all our efforts are worthwhile to provide a platform for communication and sharing of outstanding scientific results and reinforce the discipline position of animal models and experimental medicine.

Exploration of the Characteristics of Animal Supply and Demand in University Experimental Teaching Pratice

The supply and demand of laboratory animals for teaching in colleges and universities has its own internal characteristics.To grasp the supply and demand characteristics of laboratory animals for teaching is of vital importance to the planning,supply and use of teaching animals,the realization of teaching objectives and the completion of teaching tasks.Based on the supply of teaching experimental animals and the work of animal experimental teaching in our university in recent years,this paper expounds the inherent characteristics and practice of supply and demand of teaching experimental animals.

Large animal models for Huntington's disease research

Huntington'sdisease(HD)isahereditary neurodegenerative disorder for which there is currently no effectivetreatmentavailable.Consequently,the development of appropriate disease models is critical to thoroughly investigate disease progression.The genetic basis of HD involves the abnormal expansion of CAG repeats in the huntingtin(HTT)gene,leading to the expansion of a polyglutamine repeat in the HTT protein.Mutant HTT carrying the expanded polyglutamine repeat undergoes misfolding and forms aggregates in the brain,which precipitate selective neuronal loss in specific brain regions.Animal models play an important role in elucidating the pathogenesis of neurodegenerative disorders such as HD and in identifying potential therapeutic targets.Due to the marked species differences between rodents and larger animals,substantial efforts have been directed toward establishing large animal models for HD research.These models are pivotal for advancing the discovery of novel therapeutic targets,enhancing effective drug delivery methods,and improving treatment outcomes.We have explored the advantages of utilizing large animal models,particularly pigs,in previous reviews.Since then,however,significant progress has been made in developing more sophisticated animal models that faithfully replicate the typical pathology of HD.In the current review,we provide a comprehensive overview of large animal models of HD,incorporating recent findings regarding the establishment of HD knock-in(KI)pigs and their genetic therapy.We also explore the utilization of large animal models in HD research,with a focus on sheep,non-human primates(NHPs),and pigs.Our objective is to provide valuable insights into the application of these large animal models for the investigation and treatment of neurodegenerative disorders.