Era of the 4D animal model

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.

Current state of research on non-human primate models of Alzheimer’s disease

With the increasingly serious aging of the global population, dementia has already become a severe clinical challenge on a global scale. Dementia caused by Alzheimer’s disease(AD) is the most common form of dementia observed in the elderly, but its pathogenetic mechanism has still not been fully elucidated. Furthermore, no effective treatment strategy has been developed to date, despite considerable efforts. This can be mainly attributed to the paucity of animal models of AD that are sufficiently similar to humans. Among the presently established animal models, non-human primates share the closest relationship with humans, and their neural anatomy and neurobiology share highly similar characteristics with those of humans. Thus, there is no doubt that these play an irreplaceable role in AD research. Considering this, the present literature on non-human primate models of AD was reviewed to provide a theoretical basis for future research.

Advances in pig models of human diseases

Animal models of human diseases play a critical role in medical research.Pigs are anatomically and physiologically more like humans than are small rodents such as mice,making pigs an attractive option for modeling human diseases.Advances in recent years in genetic engineering have facilitated the rapid rise of pig models for use in studies of human disease.In the present review,we summarize the current status of pig models for human cardiovascular,metabolic,neurodegenerative,and various genetic diseases.We also discuss areas that need to be improved.Animal models of human diseases play a critical role in medical research.Advances in recent years in genetic engineering have facilitated the rapid rise of pig models for use in studies of human disease.In the present review,we summarize the current status of pig models for human cardiovascular,metabolic,neurodegenerative,various genetic diseases and xenotransplantation.

MicroRNAs as disease progression biomarkers and therapeutic targets in experimental autoimmune encephalomyelitis model of multiple sclerosis

Multiple sclerosis is an autoimmune neurodegenerative disease of the central nervous system characterized by pronounced inflammatory infiltrates entering the brain,spinal cord and optic nerve leading to demyelination.Focal demyelination is associated with relapsing-remitting multiple sclerosis,while progressive forms of the disease show axonal degeneration and neuronal loss.The tests currently used in the clinical diagnosis and management of multiple sclerosis have limitations due to specificity and sensitivity.MicroRNAs(miRNAs)are dysregulated in many diseases and disorders including demyelinating and neuroinflammatory diseases.A review of recent studies with the experimental autoimmune encephalomyelitis animal model(mostly female mice 6–12 weeks of age)has confirmed miRNAs as biomarkers of experimental autoimmune encephalomyelitis disease and importantly at the pre-onset(asymptomatic)stage when assessed in blood plasma and urine exosomes,and spinal cord tissue.The expression of certain miRNAs was also dysregulated at the onset and peak of disease in blood plasma and urine exosomes,brain and spinal cord tissue,and at the post-peak(chronic)stage of experimental autoimmune encephalomyelitis disease in spinal cord tissue.Therapies using miRNA mimics or inhibitors were found to delay the induction and alleviate the severity of experimental autoimmune encephalomyelitis disease.Interestingly,experimental autoimmune encephalomyelitis disease severity was reduced by overexpression of miR-146a,miR-23b,miR-497,miR-26a,and miR-20b,or by suppression of miR-182,miR-181c,miR-223,miR-155,and miR-873.Further studies are warranted on determining more fully miRNA profiles in blood plasma and urine exosomes of experimental autoimmune encephalomyelitis animals since they could serve as biomarkers of asymptomatic multiple sclerosis and disease course.Additionally,studies should be performed with male mice of a similar age,and with aged male and female mice.

Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

AIM: To establish a relevant animal model of human gastrointestinal cancer, which can be used for repetitive investigations, so as to improve our understanding and management of carcinogenesis and cancer metastasis. METHODS: Intact tissues of human colorectal and pancreatic cancers were transplanted in nude mice. The biological characteristics of the original and the corresponding transplanted tumors were investigated by HE staining, PAS staining and immunostaining. The metastases in the livers and lungs of nude mice were investigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers. RESULTS: There were totally 9 of 16 surgical specimens growing in nude mice subcutaneously and/or orthotopically (4 of 6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissue specimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumor tissues with greater than 50% tumor cell content, the success rate of the transplantation was 100% (3 cases of pancreatic cancer and 3 cases of colorectal cancer). The orthotopically trans-planted tumors resemble the original tumor morphologically and biologically, including TAA expression such as CEA by immunohistochemistry, and CEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, are associated with the potential of tumor growth in nude mice. Micrometastases in the lungs and livers of tumor bearing mice can be detected by immunostaining with biotinylated mab KL-1 and CK20-specific RT-PCR. CONCLUSION: An orthotopic transplantation model for human colon and pancreatic cancer in nude mice has been set up. We have also established sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCR to study xenotransplanted human cancer and its metastatic cancer cells in the liver and lung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and in developing new diagnostic methods and therapeutic strategies for metastases including micrometastases.

Transplantation of human hepatocytes into tolerized genetically immunocompetent rats

AIM: To determine whether normal genetically immunocompetent rodent hosts could be manipulated to accept human hepatocyte transplants with long term survival without immunosuppression. METHODS: Tolerance towards human hepatocytes was established by injection of primary human hepatocytes or Huh7 human hepatoma cells into the peritoneal cavities of fetal rats. Corresponding cells were subsequently transplanted into newborn rats via intrasplenic injection within 24h after birth. RESULTS: Mixed lymphocyte assays showed that spleen cells from non-tolerized rats were stimulated to proliferate when exposed to human hepatocytes, while cells from tolerized rats were not. Injections made between 15 d and 17 d of gestation produced optimal tolerization. Transplanted human hepatocytes in rat livers were visualized by immunohistochemical staining of human albumin. By dot blotting of genomic DNA in livers of tolerized rats 16 weeks after hepatocyte transplantation, it was found that approximately 2.5 X 10(5) human hepatocytes survived per rat liver. Human albumin mRNA was detected in rat livers by RT-PCR for 15 wk, and human albumin protein was also detectable in rat serum. CONCLUSION: Tolerization of an immuno-competent rat can permit transplantation, and survival of functional human hepatocytes.

A novel transgenic mouse model of Chinese CharcotMarie-Tooth disease type 2L

We previously found that the K141N mutation in heat shock protein B8 （HSPB8） was responsible for Charcot-Marie-Tooth disease type 2L in a large Chinese family. The objective of the present study was to generate a transgenic mouse model bearing the K141N mutation in the human HSPB8 gene, and to determine whether this K141NHSPB8 transgenic mouse model would manifest the clinical phenotype of Charcot-Marie-Tooth disease type 2L, and consequently be suitable for use in studies of disease pathogenesis. Transgenic mice overexpressing K141N HSPB8 were generated using K141N mutant HSPB8 cDNA cloned into a pCAGGS plasmid driven by a human cytomegalovirus expression system. PCR and western blot analysis confirmed integration of the KI41NHSPB8 gene and widespread expression in tissues of the transgenic mice. The K141N HSPB8 transgenic mice exhibited decreased muscle strength in the hind limbs and impaired motor coordination, but no obvious sensory disturbance at 6 months of age by behavioral assessment. Electrophysiological analysis showed that the compound motor action potential amplitude in the sciatic nerve was significantly decreased, but motor nerve conduction velocity remained normal at 6 months of age. Pathological analysis of the sciatic nerve showed reduced myelinated fiber density, notable axonal edema and vacuolar degeneration in K141N HSPB8 transgenic mice, suggesting axonal involvement in the peripheral nerve damage in these animals. These findings indicate that the KI4mHSPB8 transgenic mouse successfully models Charcot-Marie-Tooth disease type 2L and can be used to study the pathogenesis of the disease.

Application of Finite Element Analysis in Biomechanical Research of Degenerative Diseases of Lumbar Spine

As the elderly population continues to grow, the number of patients with low back pain is gradually increasing. Among them, Lumbar Degenerative Diseases (LDD) is one of the major contributors to low back pain. Biomechanical in vivo studies of the lumbar spine are mainly performed by implants or imaging data to record the real-time changes of form and stress on the intervertebral disc during motion. However, the current developments are slow due to the technological and ethical limitations. In vitro experiments include animal experiments and cadaver experiments, which are difficult to operate or differ greatly from normal human structures, and the results still need to be verified repeatedly to test their accuracy. As for finite element method, it is relatively low cost and can repeat the experimental results. Therefore, we believe that finite element analysis plays an extremely important role in biomechanical research, especially in analyzing the relationship between different surgical models and the degeneration caused by different mechanics.

Establishment of a mdr1 Multidrug Resistant Model of Orthotopic Transplantation of Liver Carcinoma on Nude Mice

To develop a new method of inducing mdrl multidrug resistance by establishinga nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominalchemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injectedsubcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice wereimplanted under the envelope of the mice liver and induced by abdominal chemotherapy withPharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were usedto examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expressionof mdr1-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, therate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfullywas 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNAand the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively.Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopicliver neoplasm coupled to chemotherapy.

Preliminary study on the production of transgenic mice harboring hepatitis B virus X gene

AIM To establish transgenic mice lineage xharboring hepatitis B virus X gene and to provide an efficient animal model for studying the exact role of the HBx gene in the process of hepatocarcinogenesis. METHODS The HBx transgenic mice were produced by microinjecting the construct with X gene of HBV (subtype adr) DNA fragment into fertilized eggs derived from inbred C57 BL/6 strain; transgenic mice were identified by using Nested PCR; expression and phenotype of HBx gene were analyzed in liver from transgenic mice at the age of 8 weeks by RT PCR, pathologic examination and periodic acid schiff staining (PAS), respectively. RESULTS Five hundred and fourteen fertilized eggs of C57 BL/6 mice were microinjected with recombinant retroviral DNA fragment, and 368 survival eggs injected were transferred to the oviducts of 18 pseudopregnant recipient mice, 8 of them became pregnant and gave birth to 20 F1 offspring. Of 20 offsprings, four males and two females carried the hybrid gene (HBx gene). Four male mice were determined as founder, named X1, X5, X9 and X15. These founders were back crossed to set up F1 generations with other inbred C57BL/6 mice or transgenic littermates, respectively. Transmission of HBx gene in F1 offspring of X1, X5 and X9 except in X15 followed Mendelian rules. The expression of HBx mRNA was detected in liver of F1 offspring from the founder mice (X1 and X9), which showed vacuolation lesion and glycogen positive foci. CONCLUSION Transgenic mice harboring HBx gene were preliminarily established.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

Inhibiting effect of antisense oligonucleotides phosphorthioate on gene expression of TIMP-1 in rat liver fibrosis

AIM: To observe the inhibition of antisense oligonucleotides (asON) phosphorthioate to the tissue inhibitors metalloproteinase-1 (TIMP-1) gene and protein expression in the liver tissue of immunologically induced hepatic fibrosis rats. The possibility of reversing hepatic fibrosis through gene therapy was observed. METHODS: Human serum albumin (HSA) was used to attack rats, as hepatic fibrosis model, in which asONs were used to block the gene and protein expressing TIMP-1. According to the analysis of modulator, structure protein, coding series of TIMP-1 genome, we designed four different asONs. These asONs were injected into the hepatic fibrosis models through coccygeal vein. The results was observed by RT-PCR for measuring TIMP-1 mRNA expression, immunohistochemistry and in situ hybridization for collagen I, II, special staining of collagen fiber, and electron microscopic examination. RESULTS: Hepatic fibrosis could last within 363 days in our modified model. The expressing level of TIMP-1 was high during hepatic fibrosis process. It has been proved by the immunohistochemical and the electron microscopic examination that the asON phosphorthioate of TIMP-1 could exactly express in vivo. The effect of colchicine was demonstrated to inhibit the expressing level of mRNA and the content of collagen I, III in the liver of experimental hepatic fibrosis rats. However, the electron microscopy research and the pathologic grading of hepatic fibrosis showed that there was no significant difference between the treatment group and the model group (P】 0.05). CONCLUSION: The experimental rat model of hepatic fibrosis is one of the preferable models to estimate the curative effect of anti-hepatic fibrosis drugs. The asON phosphorthioate of TIMP-1 could block the gene and protein expression of TIMP-1 in the liver of experimental hepatic fibrosis rats at the mRNA level. It is possible to reverse hepatic fibrosis, and it is expected to study a new drug of antihepatic fibrosis on the genetic level. Colchicine has very limited therapeutic effect on hepatic fibrosis, furthermore, its toxicity and side effects are obvious.

Metastatic human hepatocellular carcinoma models in nude mice and cell line with metastatic potential

Metastatic human HCC model is needed for the studies on mechanism and intervention of metastatic recurrence. By using orthotopic implantation of histologically intact tissues of 30 surgical specimens, a patient-like metastatic model of human HCC in nude mice (LCI-D20) and a low metastatic model of human HCC in nude mice (LCI-D35) have been established. All mice with transplanted LCI-D20 tumors exhibited extremely high metastatic ability including spontaneous metastasis to liver, lungs, lymph nodes and peritoneal seeding. Remarkable difference was also found in expression of some of the invasiveness related genes and growth factors between the LCI-D20 and LCI-D35 tumors. PAI-1 increased gradually following tumor progression in LCI-D20 model, and correlated with tumor size and AFP level. Phasic expression of tissue intercellular adhesion molecule-1 in this model was also observed. Using corneal micropocket model, it was demonstrated that the vascular response induced by LCI-D20 tumor was stronger than that induced by LCI-D35 tumor. Similar report on metastatic human HCC model in nude mice and human HCC cell line with metastatic potential was rarely found in the literature. This LCI-D20 model has been widely used for the studies on intervention of metastasis, including anti-angiogenesis,antisense approach, metalloproteinase inhibitor, differentiation inducer, etc. It is concluded that the establishment of metastatic human HCC model in nude mice and human HCC cell line with metastatic potential will provide important models for the in vitro and in vitro study of HCC invasiveness, angiogenesis as well as intervention of HCC recurrence.

Therapeutic opportunities and challenges of induced pluripotent stem cells-derived motor neurons for treatment of amyotrophic lateral sclerosis and motor neuron disease

Amyotrophic lateral sclerosis（ALS） and motor neuron diseases（MNDs） are progressive neurodegenerative diseases that affect nerve cells in the brain affecting upper and lower motor neurons（UMNs/LMNs）, brain stem and spinal cord. The clinical phenotype is characterized by loss of motor neurons（MNs）, muscular weakness and atrophy eventually leading to paralysis and death due to respiratory failure within 3–5 years after disease onset. No effective treatment or cure is currently available that halts or reverses ALS and MND except FDA approved drug riluzole that only modestly slows the progression of ALS in some patients. Recent advances in human derived induced pluripotent stem cells have made it possible for the first time to obtain substantial amounts of human cells to recapitulate in vitro “disease in dish” and test some of the underlying pathogenetic mechanisms involved in ALS and MNDs. In this review, I discussed the opportunities and challenges of induced pluropotent stem cells-derived motor neurons for treatment of ALS and MND patients with special emphasis on their implications in finding a cure for ALS and MNDs.

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

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.

Formulation of Mathematical Model for TB Transmission in Zoonotic Areas with Existence of Endemic Equilibrium

A mathematical model incorporating animal TB and Human TB transmission is formulated and analysed in order to determine the role of animal TB and human TB in the overall TB transmission and also, to determine the parameters which govern the transmission of the TB disease. The model has five classes namely susceptible, exposed animal TB, and exposed human TB, infectious and recovery. The model assumed that there are two classes for infected individuals, those who acquired TB through animal and those who acquire TB from human. Qualitative results show that the model has the disease-free equilibrium and at least one endemic equilibrium that is locally asymptotically stable. The study includes numerical simulations as a way of supporting the analytical results. Graphical results indicate that animal TB has major contribution on overall TB transmission and the TB transmission can be reduced by ensuring intervention to both Animal TB and Human TB. Furthermore the equations indicate that there is at least one endemic equilibrium which translates that t animal and human have the contribution on TB transmission. This shows that both animals and humans together with fast progressors have contribution on TB transmissions.

An everlasting role of animal models in understanding human disease

Model organisms have been widely used to dissect important biological phenomena, as well as to explore potential causes and treatments for human disorders. Much of our knowledge on molecular mechanisms underlying the heredity, development as well as physiology is largely derived from the researches of model organisms. We have witnessed an explosive increase in the development and application of genetic modified model organisms in the last decade.

Genetically Modified Pig Models for Human Diseases

Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases,

扩张型心肌病动物模型及治疗的研究进展

扩张型心肌病(dilated cardiomyopathy,DCM)是一类以一侧或双侧心室扩张和收缩功能障碍为特征的心血管疾病,发病原因包括遗传性的基因突变及多种继发因素。人类DCM动物模型涉及小鼠、大鼠、斑马鱼、猪等多种实验动物,一般通过基因编辑、药物诱导、自身免疫缺陷诱导、病毒感染等方法构建。借助DCM动物模型,研究者对该病的致病机制和治疗靶点进行了深入的研究。本文简述了人类DCM的病理特征、临床症状和流行病学特征,对近年来DCM动物模型的种类和构建方法进行了综述,并对优化造模方法与推动治疗研究提出了新的展望。基于DCM动物模型的治疗研究可以帮助我们更好地理解DCM的发生机制,为开发新的治疗方法提供依据。

基于基因编辑技术的动物疾病模型构建与应用研究

该文综述了基于基因编辑技术的动物疾病模型的构建与应用研究,特别关注牛羊大牲畜领域。随着基因编辑技术的不断发展,基因编辑动物疾病模型在生物医学研究中扮演着越来越重要的角色。介绍了不同疾病模型的特点、构建方法以及在相关领域的应用情况。通过阐述,将更深入地了解基因编辑技术在动物疾病模型构建和防疫工作中的潜力和价值。