1.Functions and physiological roles of two types of estrogen receptors, ERalpha and ERbeta, identified by estrogen receptor knockout mouse.
Hye Rim LEE ; Tae Hee KIM ; Kyung Chul CHOI
Laboratory Animal Research 2012;28(2):71-76
Estrogens, a class of steroid hormones, regulate the growth, development, and physiology of the human reproductive system. Estrogens also involve in the neuroendocrine, skeletal, adipogenesis, and cardiovascular systems. Estrogen signaling pathways are selectively stimulated or inhibited depending on a balance between the activities of estrogen receptor (ER) alpha or ERbeta in target organs. ERs belong to the steroid hormone superfamily of nuclear receptors, which act as transcription factors after binding to estrogen. The gene expression regulation by ERs is to modulate biological activities, such as reproductive organ development, bone modeling, cardiovascular system functioning, metabolism, and behavior in both females and males. Understanding of the general physiological roles of ERs has been gained when estrogen levels were ablated by ovariectomy and then replenished by treatment with exogenous estrogen. This technique is not sufficient to fully determine the exact function of estrogen signaling in general processes in living tissues. However, a transgenic mouse model has been useful to study gene-specific functions. ERalpha and ERbeta have different biological functions, and knockout and transgenic animal models have distinct phenotypes. Analysis of ERalpha and ERbeta function using knockout mouse models has identified the roles of estrogen signaling in general physiologic processes. Although transgenic mouse models do not always produce consistent results, they are the useful for studying the functions of these genes under specific pathological conditions.
Adipogenesis
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Animals
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Animals, Genetically Modified
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Cardiovascular System
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Estrogen Receptor alpha
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Estrogen Receptor beta
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Estrogens
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Female
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Gene Expression Regulation
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Humans
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Male
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Mice
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Mice, Knockout
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Mice, Transgenic
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Ovariectomy
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Phenotype
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Receptors, Cytoplasmic and Nuclear
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Receptors, Estrogen
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Transcription Factors
2.Current status and perspective of hepatitis C virus models.
Si-hai ZHAO ; Yong-lie CHU ; Meng XUN
Journal of Zhejiang University. Medical sciences 2007;36(6):614-619
Lack of proper study models has brought difficulties in the study of the mechanism of viral infection, life cycle and pathogenic mechanism of hepatitis C virus (HCV) and also become the major obstacles in development of efficient vaccine and new drugs for hepatitis C. In recent years, the establishment of robust HCV cell culture infection system and HCV transgenic animal provide powerful tools for the analysis of host virus interactions, which facilitate the discovery of antiviral drugs and vaccines for this important human pathogen.
Animals
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Animals, Genetically Modified
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virology
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Disease Models, Animal
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Genotype
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Hepacivirus
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genetics
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Hepatitis C
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virology
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Mice
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Mice, Transgenic
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virology
3.Impaired cognitive map in transgenic animals relevant to Alzheimer's disease: from neurons to network.
Li ZHENG ; Ling WANG ; Jia-Jia YANG ; Chen-Guang ZHENG
Acta Physiologica Sinica 2023;75(5):671-681
Alzheimer's disease (AD) is a typical cognitive disorder with an increasing incidence in recent years. AD is also one of the main causes of disability and death of the elderly in current aging society. One of the most common symptoms of AD is spatial memory impairment, which occurs in more than 60% of patients. This memory loss is closely related to the impairment of cognitive maps in the brain. The entorhinal grid cells and the hippocampal place cells are important cellular basis for spatial memory and navigation functions in the brain. Understanding the abnormal firing pattern of these neurons and their impaired coordination to neural oscillations in transgenic rodents is crucial for identifying the therapeutic targets for AD. In this article, we review recent studies on neural activity based on transgenic rodent models of AD, with a focus on the changes in the firing characteristics of neurons and the abnormal electroencephalogram (EEG) rhythm in the entorhinal cortex and hippocampus. We also discuss potential cell-network mechanism of spatial memory disorders caused by AD, so as to provide a scientific basis for the diagnosis and treatment of AD in the future.
Animals
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Mice
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Alzheimer Disease/genetics*
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Animals, Genetically Modified
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Cognition
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Cognitive Dysfunction
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Hippocampus/physiology*
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Memory Disorders
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Mice, Transgenic
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Neurons/physiology*
4.Retrospect and prospect of transgenic fish breeding in China.
Chinese Journal of Biotechnology 2016;32(7):851-860
The first transgenic fish was generated in China about 30 years ago. Since then, considerable progress has been achieved for farmed fishes breeding with improvement of target traits of growth, disease resistance, stress tolerance, and nutrition qualities. Up to now, the technology of transgenic fish breeding is almost mature and the biosafety assessment is established. In this review, a successful example of the fast-growing transgenic common carp was presented and the foreground of transgenic fish breeding was also discussed and prospected.
Animals
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Animals, Genetically Modified
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Breeding
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China
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Fishes
5.Mouse Model for the Research of Sinusitis Induced Olfactory Dysfunction.
Korean Journal of Otolaryngology - Head and Neck Surgery 2015;58(12):815-821
Olfactory dysfunction is one of the most debilitating problem in chronic rhinosinusitis (CRS) patients, and exact mechanism underlying sinusitis induced olfactory dysfunction was not fully understood. In vivo manipulation for olfactory epithelium and fresh specimen for histopathological analysis are essential for research, but it is nearly impossible to do in human due to inaccessibility of olfactory epithelium and risk for complication. For this reason, several animal models using toxic materials, such as 3-methylindole or bromomethane, have been suggested for mimicking olfactory epithelial damage in CRS, but none of them could truly imitate the event which happens in real patient. Inducible olfactory inflammation (IOI) mouse is a transgenic mouse model selectively producing tumor necrosis factor-alpha (TNF-alpha) in sustentacular cell of olfactory epithelium. The production of TNF-alpha can be actively initiated by giving food containing doxycycline to IOI mouse, and inflammation is stopped in the absence of doxycycline. Both toxicity model and transgenic model have their own advantages and disadvantages, therefore appropriate model should be selected for optimal results.
Animals
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Animals, Genetically Modified
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Doxycycline
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Humans
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Inflammation
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Mice*
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Mice, Transgenic
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Models, Animal
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Olfactory Mucosa
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Sinusitis*
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Skatole
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Smell
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Tumor Necrosis Factor-alpha
6.The in vivo imaging of zebrafish for chemical vascular toxicity assessment.
Di JI ; Qi Cheng ZHU ; Yan Hong WEI
Chinese Journal of Preventive Medicine 2022;56(1):33-37
Objective: To evaluate the vascular toxicity of chemicals by a real-time observation approach using the transgenic zebrafish. Methods: The spatiotemporal vascular alterations of transgenic zebrafish after chemical exposure were assessed by laser confocal microscopy and high-content screening analysis, respectively. Results: The method using Laser Confocal Microscopy (LCM) is easier to operate and yields high-resolution images, while it is lower throughput and inefficient. In contrast, high-content analysis (HCA) analysis obtains high-quality data of vascular toxicity manifesting whole blood vasculature, whereas it requires delicate operation procedures and advanced experimental conditions. Conclusion: Two kinds of zebrafish imaging methods each have advantages and disadvantages. LCM is suitable for the evaluation of a small number of chemicals. HCA, a cutting-edge technology, has great potential for chemical safety assessment allowing high throughput vascular toxicity tests of a good number of chemicals at a time.
Animals
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Animals, Genetically Modified
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Cardiovascular System
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Toxicity Tests
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Zebrafish
7.Advances in tumor-therapy using genetically modified Salmonella.
Kang LIANG ; Xinxin ZHAO ; Jie YI ; Qiong LIU ; Qing LIU ; Qingke KONG
Chinese Journal of Biotechnology 2016;32(5):565-576
Tumor is a neoplasm formed by the abnormal proliferation of local tissue cells under the effects of different tumorigenic factors. Tumor-therapy has always been a difficult clinical issue, while regular cancer treatments, such as radiotherapy, chemotherapy and surgery, have obvious limitations. Earlier studies have shown that some obligate anaerobes or facultative anaerobes have anti-tumor effects, for example, Salmonella typhymurium as facultative anaerobic bacteria can selectively colonize tumors and inhibit their growth. Besides, Salmonella has many advantages in tumor-therapy. In the past decade or two, many researchers have carried out genetic manipulation to attenuate the virulence of Salmonella, to improve their specificity of tumor colonization and specially to use attenuated Salmonella as carriers to deliver a variety of anti-tumor therapeutic molecules, and these genetically modified Salmonella have shown good anti-tumor effects in many animal experiments. Along with further research of Salmonella-mediated antitumor treatment, applications of genetically modified Salmonella for more effective tumor-therapy are promising. We reviewed the anti-tumor mechanisms of Salmonella, the research progress in tumor-therapy using genetically modified Salmonella, and current problems and possible solutions.
Animals
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Humans
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Microorganisms, Genetically-Modified
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Neoplasms
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therapy
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Salmonella
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genetics
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Virulence
8.Construction of "lock-key" biological living material based on double engineered bacteria and its application on intestinal retention in vivo.
Minghui ZHANG ; Yingying ZHANG ; Pengcheng ZHAO ; Hanjie WANG
Chinese Journal of Biotechnology 2023;39(3):1163-1174
At present, the research of biological living materials mainly focuses on applications in vitro, such as using a single bacterial strain to produce biofilm and water plastics. However, due to the small volume of a single strain, it is easy to escape when used in vivo, resulting in poor retention. In order to solve this problem, this study used the surface display system (Neae) of Escherichia coli to display SpyTag and SpyCatcher on the surface of two strains, respectively, and constructed a double bacteria "lock-key" type biological living material production system. Through this force, the two strains are cross-linked in situ to form a grid-like aggregate, which can stay in the intestinal tract for a longer time. The in vitro experiment results showed that the two strains would deposit after mixing for several minutes. In addition, confocal imaging and microfluidic platform results further proved the adhesion effect of the dual bacteria system in the flow state. Finally, in order to verify the feasibility of the dual bacteria system in vivo, mice were orally administrated by bacteria A (p15A-Neae-SpyTag/sfGFP) and bacteria B (p15A-Neae-SpyCatcher/mCherry) for three consecutive days, and then intestinal tissues were collected for frozen section staining. The in vivo results showed that the two bacteria system could be more detained in the intestinal tract of mice compared with the non-combined strains, which laid a foundation for further application of biological living materials in vivo.
Animals
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Mice
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Bacteria
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Microorganisms, Genetically-Modified
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Escherichia coli/genetics*
9.Agricultural biotechnology safety assessment.
Scott MCCLAIN ; Wendelyn JONES ; Xiaoyun HE ; Gregory LADICS ; Andrew BARTHOLOMAEUS ; Alan RAYBOULD ; Petra LUTTER ; Haibin XU ; Xue WANG
Chinese Journal of Preventive Medicine 2015;49(1):78-87
Genetically modified (GM) crops were first introduced to farmers in 1995 with the intent to provide better crop yield and meet the increasing demand for food and feed. GM crops have evolved to include a thorough safety evaluation for their use in human food and animal feed. Safety considerations begin at the level of DNA whereby the inserted GM DNA is evaluated for its content, position and stability once placed into the crop genome. The safety of the proteins coded by the inserted DNA and potential effects on the crop are considered, and the purpose is to ensure that the transgenic novel proteins are safe from a toxicity, allergy, and environmental perspective. In addition, the grain that provides the processed food or animal feed is also tested to evaluate its nutritional content and identify unintended effects to the plant composition when warranted. To provide a platform for the safety assessment, the GM crop is compared to non-GM comparators in what is typically referred to as composition equivalence testing. New technologies, such as mass spectrometry and well-designed antibody-based methods, allow better analytical measurements of crop composition, including endogenous allergens. Many of the analytical methods and their intended uses are based on regulatory guidance documents, some of which are outlined in globally recognized documents such as Codex Alimentarius. In certain cases, animal models are recommended by some regulatory agencies in specific countries, but there is typically no hypothesis or justification of their use in testing the safety of GM crops. The quality and standardization of testing methods can be supported, in some cases, by employing good laboratory practices (GLP) and is recognized in China as important to ensure quality data. Although the number of recommended, in some cases, required methods for safety testing are increasing in some regulatory agencies, it should be noted that GM crops registered to date have been shown to be comparable to their nontransgenic counterparts and safe . The crops upon which GM development are based are generally considered safe.
Agriculture
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Animal Feed
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Animals
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Biotechnology
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China
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Consumer Product Safety
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Food, Genetically Modified
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Humans
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Models, Animal
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Plants, Genetically Modified
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Safety
10.Biosafety assessment of genetically engineered animals: a review.
Chinese Journal of Biotechnology 2012;28(3):267-281
With the research and development of genetically engineered animals (GEAs) in breeding of new variety, xenotransplantation, bioreactor and disease model, biosafety issues of GEAs have attracted widespread attentions worldwide. So far, governments and agencies have established corresponding laws and regulations to regulate research and application of GEAs or their derived products. We reviewed research contents, evaluated principles, policies and procedures for biosafety of GEAs, also enumerated upcoming approved products of GEAs. Finally, we suggested perspectives of research and application of GEAs or their derived products.
Agriculture
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economics
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legislation & jurisprudence
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Animals
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Animals, Genetically Modified
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genetics
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growth & development
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Biotechnology
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economics
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legislation & jurisprudence
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Food Safety
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Food, Genetically Modified
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economics
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standards
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Laboratories
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standards