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.

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.

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.

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.

Modifi cation of sleep architecture in an animal model of experimental cirrhosis

AIM： To analyze the polygraphic sleep patterns during cirrhosis progression in a rat model by repeated CCh administration. METHODS： Male Wistar rats received three weekly injections of CCl4 for 11 wk, and were analyzed before and during the induction of cirrhosis. Rats were im- planted with electrodes to record their sleep patterns. Polygraph recordings were made weekly over 11 wk for 8 h, during the light period. After a basal recording, rats received three weekly injections of CCl4. Histological confirmation of cirrhosis was performed after 11 wk. RESULTS： The results showed a progressive decrease in total wake time that reached statistical significance from the second week of treatment. In addition, there was an increase in total time of slow wave sleep （SWS）Ⅱ and rapid eye movement sleep （REM sleep） in most of the 11 wk. SWS I showed no significant variations. During the final weeks, a significant increase in REM sleep frequency was also observed. Histological analyses of the livers showed unequivocal signs of cirrhosis. CONCLUSION： These data suggest that hepatic failure produced by CCh administration is capable of modifying the sleep pattern even after only a few doses.

DNA Damage after Ozone-Photodynamic Therapy in Cancer Animals： Experimental Research

Objectives： To assess the genotoxic effect of a new antitumor ozone-photodynamic therapy using the improvedmodification of the COMET assay. Methods： Xenograft cancer models on 58 rats were used. The sarcoma RA was transplantedsubcutaneously, and after increasing of tumor volume from 0.5 to 4.2 cm3, rats were divided into the four groups： ＂Intact＂--healthy,＂Control＂--with xenografted tumors and no treatment, ＂PDT＂--the rats treated with the photodynamic therapy, ＂PDT ＋ozone＂--the rats were treated with both photodynamic therapy and injections of ozonated saline solution. The toxicity of treatmentwas assessed by DNA damage in leukocytes using the new modification of the COMET assay. The analysis of the ＂COMETs＂ wasperformed following the percentage of DNA in the tail of the ＂COMET＂ （% TDNA）. Results： A combination of PDT and ozonemakes the strongest negative impact on tumor growth. The tumor growth inhibition is associated with low genotoxic exposure ofozone-photodynamic therapy on whole blood leukocytes of cancer rats. Conclusions： A new modification of the COMET assay canprovide the assessment of the genotoxic effect of the antitumor therapy in experimental neoplasia.

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.

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.

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.

An experimental proposal for low order laboratory animals’ extension of metabolic life

Essential bibliography, with therein references included, is presented owing to the contribution of the author groups to Mitochondrial Filamentation, which is a new emerging field of physiological energy metabolism. These studies provide the first seed concept for trials to extend the metabolic life, for a few days, in low order laboratory mammals killed by electrocution, as a first type of accidental death. It is proposed, essentially, to cool out the corpses very soon after death at 12oC-14oC and take advantage of the effect super magnetism to counteract the force of gravity to install a net recurrent cycle of oxygen consumption and oxygen production by filamented mitochondria in all the organism tissues. Once the cause of death had been corrected adequately, it is possible to try the reanimation to experience the full life of the corpse with highly sophisticated methodology.

Clinical Application of the Full Automatic Animal Experimental Cabin of Normobaric/Hypobaric Hypoxia and High Carbon Dioxide

Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie 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 hypoxie with high carbon dioxide enviromnent, 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 tor clinical research.

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.

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.

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.

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.

Experimental Studies on the Irradiation of Facial Bones in Animals:A Review

Introduction: Radiotherapy is often used to treat head and neck malignancies, with inevitable effects on the surrounding healthy tissues. We have reviewed the literature concerning the experimental irradiation of facial bones in animals. Materials and Methods: A PubMed search was performed to retrieve animal experiments on the irradiation of facial bones that were published between January 1992 and January 2012. The search terms were “irradiation facial bone” and “irradiation osteoradionecrosis”. Results: Thirty-six publications were included. The irradiation sources were Cobalt60, orthovoltage, 4 - 6 megavolt photons, and brachytherapy. The total dose varied between 8 - 60 Gy in single or multiple fractions. The literature presents a broad range of animal studies that differ in terms of the in vivo model, irradiation, observation period, and evaluation of results. Discussion: The different animal models used leave many questions unanswered. A detailed and standardized description of the methodology and results would facilitate the comparability of future studies.

Effect of hyperbaric oxygen on nerve impairment recovery of animals after organophosphorus:an experimental study

Objective To investigate the effect of hyperbarci oxygen(HBO) on recovery of nerves injury in rats suffered from acute organophosphorus poisoning. Method We established organophosphorus poisoning models and observed effect of HBO on recovery of injure nerves. Results Compared with control group, cerebrospinal fluid induced peak potential and incubation period in HBO group were significantly recovered(P<0.05).HBO could accelerated repair of injured nerves. Conclusion HBO could relieve injury of nerves during treatment of organophosphorus poisoning.

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.