模式动物 z-bo 2020-10-09 651

　　In the fields of life sciences and human health, the physiological and pathological processes of laboratory animals in life activities have many similarities with humans. Animal models of major human diseases have been established to analyze the causes of diseases and respond to specific populations. The process of disease susceptibility and new drug development plays an important role. However, because various model animals are very different from humans in terms of genetic levels and microbial composition in the body, the fact that disease models are close to actual diseases is the accuracy of disease biology research and drug testing and humans. It is not easy to determine the establishment of the disease to model the disease under equivalent conditions.

　　Past scientific research results show that mice are the best animal models for establishing human diseases. The researchers used ENU mutagenesis technology to obtain more than 30 mouse mutants, including cardiovascular, metabolic, cataract and aging diseases. The researchers cloned related mutant genes and these. We have discovered new drugs that use target mutants to treat diseases and are used in the screening and development of new drugs. Mice not only have physiological, biochemical and developmental processes very similar to humans, but also 90% of their genomes are homologous to humans. Therefore, the mouse model can basically simulate the etiology of human diseases and their response to drugs. 2018 (Second Session) Symposium on Model Animal Research and Application and Animal Models of Major Diseases

　　On August 15 this year, Dr. Wang Xiaodong’s research team unveiled the mystery of the aging of the male reproductive system. This study describes the discovery of a signaling pathway that controls the aging of the male reproductive system in mice, and the development of small molecule compounds that target key kinases in the aging pathway. The researchers found that cell death is caused by the membrane-bound kinase RIPK3 and its substrate MLKL. In the death process induced by tumor necrosis factor, RIP3 needs to be activated by the similar kinase RIP1. Activated RIP3 activates MLKL by phosphorylating it, leading to cell death. Male mice lacking RIP3 and MLKL and fed with RIP1 inhibitors can have longer fertilization ability, but the offspring of aging are much more than the offspring of young male mice. There is a flaw. The research was published in the online eLIFE journal. Currently, this is the first fully described aging pathway discovered at the cellular and molecular level of mammals and the overall animal level. Technology and medicine have made great progress, but the causes of most genetic diseases are poorly understood. Some studies have shown that mouse models cannot accurately simulate the human response to inflammatory diseases. In recent years, the development of gene editing technology has made the establishment of diseased animal models more accurate and faster, especially with the emergence and maturity of technologies such as ZFN, TALEN and CRISPR-Cas9, the creation of model animals has become relatively easy.　　

　　Single-cell RNA sequencing classifies Drosophila neurons

　　In a study published in the journal Cell on November 16, researchers used single-cell RNA sequencing technology to study neural classification and the technology. For the first time, Fruit Fly was applied to the olfactory neurons in the brain. In the olfactory nervous system of Drosophila, 50 types of olfactory projection nerve cells and 50 types of upstream olfactory sensory nerve cells form a one-to-one synaptic connection. Different types of olfactory projection nerve cells have very specific connections and functions. Therefore, it is an excellent model for studying neural cell classification. The researchers said that they will provide new ideas for the subsequent classification of higher animal or human nerve cells. This new single-cell RNA sequencing method of olfactory projection neurons in the Drosophila brain can be applied to other tissue cells in Drosophila or other smaller cell types in animal models. In addition, ICIM, a research-based data analysis method based on machine learning, can classify very similar cell types well and provide a reference for other similar studies.

　　China has completed the establishment and analysis of the zebrafish ADHD disease model.

　　As a model animal, the study of zebrafish has a relatively complete genetic manipulation method. The advantages of zebrafish are high genetic homology with humans (87%), large number of experimental samples, low reproduction costs, and simple experimental procedures. Recently, Liu Dong's research team from the Department of Biology of Southern University of Science and Technology published a study to reduce the expression of the zebrafish MICALL2 homologous gene mical2b. The study showed that abnormal neuron development in the juvenile brain was found/corrected by this treatment to reduce this condition. Therefore, the researchers said that MICALL2 may be the causative gene that causes the new disease of ADHD. Researchers have completed the establishment and analysis of the zebrafish ADHD disease model, and plan to use the same technology to screen ADHD candidate genes and establish mutant fish strains. Based on the successful establishment of the ADHD zebrafish model, the screening of ADHD treatment will be carried out.

　　CRISPR-Cas9 system used to construct mouse models of heart failure

　　Recently, researchers at the Southwest Medical Center's Regenerative Medicine Center have constructed mice that specifically express Cas9 in cardiomyocytes and have cardiomyocyte specificity. Using CRISPR-cas9 gene editing technology to construct a mouse heart disease model, and successfully obtain cardiomyocyte-specific myh6 gene knockout mice. This technology has important guidance for subsequent tissue-specific gene modification. The results were published in the latest issue of "PNAS Magazine". This study found that the mutant mice suffered from heart failure and abnormal hypertrophy. Compared with wild mice, the myocardial shortening rate of mutant mice was significantly reduced. Then, the researchers isolated Cas9-positive cardiomyocytes from mice and stimulated them with sgRNA in vitro. The results indicate that Myh6-specific sgRNA induction may increase and lengthen cardiomyocytes.　　

　　Scientists have successfully established a more faithful breast cancer PDX model

　　New cancer treatment methods, because animal models used for drug testing usually fail to restore the complex biological characteristics of cancer, almost 90% of them ultimately fail. Research data obtained using this inaccurate animal model often does not match humans. Recently, Swiss scientists have developed a new animal model of breast cancer that can more faithfully restore disease characteristics. After testing, the researchers believe that this is the most clinically feasible breast cancer model so far. Related research results have been published in the academic journal "Cancer Cells". Scientists have developed a heterologous transplantation mouse model that can better represent the biological characteristics of human estrogen receptor-positive breast tumors. Studies have shown that the ducts in this mouse model are estrogen receptor-positive breast tumors. The key to normal growth is that compared with traditional methods, the breast duct of this mouse model can provide a better growth and growth environment for the injected cancer cells. Injecting estrogen receptor-positive breast cancer cells into the duct of a mouse model can significantly improve the survival rate of tumor cells. To test this allogeneic transplantation model, the researchers injected breast cancer cell lines and tumor tissue from estrogen receptor-positive breast cancer patients directly into the catheter of the mouse model. The results are very exciting. Almost all xenograft models can faithfully restore the tissue physiology and even molecular biological characteristics of the patient's tumor.

　　Animal models are the foundation of modern biomedical research and the necessary strategic resources of the National Institute of Biomedical Sciences. Developed countries such as Europe, America, Japan, etc. attach great importance to them. Through various inputs, they have accumulated many model animal resources and accumulated better animal strains. Foreign researchers pay more attention to exchanges and sharing results. I am paying disease animal models as the basic of experimental medicine research. The task will face more stringent requirements to further implement the national precision medicine plan. To this end, Biology Valley hopes to promote basic medicine and translational medicine research on animal models of traditional Chinese medicine through the "2018 (Second) Animal Models and Animal Models of Major Diseases". Held "Research and Application Symposium". It laid the foundation for the establishment of a basic scientific research platform.