【Animal Modeling】-What should be paid attention to when preparing animal models of diseases?

  (1) Remember that the model needs to reproduce the required human disease as much as possible.

  When replicating an animal model of a disease, it is necessary to start with the research objectives and emphasize that you are familiar with the inducing conditions, host characteristics and symptoms of the disease. Can you get the expected results to fully understand and analyze the cause and all the information required for the animal model? Researchers also found that the induced dose required for various animals to conduct experiments, host age, sex, genetic characteristics, and the animal’s impact on histology, biochemistry, pathology, and other aspects of human diseases, you need to understand the relationship between the two Distinguish between diseases. Animal diseases similar to corresponding human organs should be avoided as model materials. In order to increase the similarity between replicated animal disease models and human diseases, it is necessary to choose as many animal models as possible that correspond to various sensitive animal and human diseases.

  (2) Pay attention to the practical value of selected animals

  The model is suitable for most researchers. It needs to be easy to replicate, easy to operate, and able to collect various specimens in experiments. At the same time, by targeting animals familiar to ordinary breeders and easy to breed, no special breeding facilities or transportation conditions are required, and it is easy to guarantee economically and technically. In addition, the source of animals must be sufficient, and it is beneficial to expand the sample, select multiple births and repeat the experiment. Especially in the case of chronic disease models, animals must have a certain survival time, which is convenient for long-term observation, and can be used to prevent their death or death due to complications after the model is completed. Animal populations used in biomedical research can be divided into three basic types, depending on their genetic makeup and the degree of environmental control by researchers. ①Experimental animals: can provide the best genetic and environmental operations. (2) Economic animals: Whether they breed in rural or urban areas, the degree of human interference is different, and the animal environment may be very close to the human environment. ③Wild animals: there is almost no human interference. Observing wildlife in the natural environment helps to correctly assess natural morbidity and mortality. However, it is difficult to maintain under recording and experimental conditions, and it poses a direct or indirect threat to humans and animals, so you should be careful when using it. Therefore, when copying models, you need to pay attention to the selection of animal populations, and understand the characteristics of different animal populations and their impact on the copied animals. It may be possible to study specific animals (carnivores, carnivores, Lagomorpha) in all three species, thereby increasing the possibility of comparative studies of environmental and genetic factors. When choosing three different animal populations to replicate animal models, you need to understand the advantages and disadvantages of each animal.

  (3) Do not blindly use inbred lines to avoid uncontrollable factors entering the experiment

  inbred lines have a clear genetic background, uniform response and small individual differences. When widely used to replicate animal models, please carefully consider the following factors that need to be designed: 1. The inbreeding method is different from the natural state. For example, spontaneously diabetic BB rats and Wistar mice have clinical features of diabetes, but in practice, they are usually associated with severe peripheral nervous system diseases, testicular atrophy, thyroiditis, malignant lymphoma, etc. Use inbred lines. 2.2. The sublines formed by inbred lines are not the same line, so it is necessary to fully understand the characteristics and related information of the new line. 3.3. The resulting strain will mutate. Even in the strains that form the model, genetic mutations and genetic drift may occur due to reproduction and environmental changes. In other words, there is a risk of mutation and damage. 4.4. The F1 between two inbred species is usually used as a model. F1 individuals have good homogeneity and strong resistance to experiments, which makes up for the defects of inbred lines. Except for close relatives and F1, the reproducibility and consistency between individuals is not as good as that of close relatives and F1 animals, but close relatives have relatively stable genetic characteristics and responsiveness, strong vitality, high reproduction rate and disease resistance. Can be mass produced.

  (4) Correctly evaluate animal disease models

  It is necessary to understand that there is no animal model that can fully reproduce the actual situation of animal diseases. After all, animals are not the epitome of the human body. Model experiments are only indirect studies, and may only resemble human diseases in some or some aspects. Therefore, the correctness of the model experiment conclusions is only relative and must be verified by the human body. If something different from human disease occurs during the replication process, the degree and extent of the difference must be analyzed, parallel common points must be found, and the value of this value must be correctly evaluated.

  (5) The high level of animal evolution does not mean that all organs and functions are close to the human level

  When the animal model is copied when conditions permit. As much as possible, we should consider using highly evolved animals similar to humans as models. However, the higher the degree of evolution, the closer the distance between all the organs and functions of animals and humans. For example, when non-human primates induce atherosclerosis, the lesions are usually in small arteries, and even if they appear in the aorta, their distribution is different from that of humans. According to reports, when a pigeon is used as a model, the macular area of the thoracic aorta can reach 10%, and the microscopic changes are similar to humans, so it is widely used by researchers. (6) Use comparative medicine to conduct analog research and correctly analyze the results of animal experiments

  Animals and humans share a common evolutionary origin. From the simplest single-celled organisms to the best humans, their most basic component is protein, which shares nucleic acid and a set of genetic coding systems. Although there are countless species in nature, the life world is essentially continuous, so the basic principles of various life phenomena are very consistent. Because animals and humans share evolutionary homology and genetic homogeneity, it is possible to replicate models that mimic the symptoms of human diseases in laboratory animals. This is the genetic, molecular and biological basis of comparative medicine. Take mice as an example. Humans and mice look very different, but almost all mice have human homologous genes, and their disease phenotypes are very similar to humans. The ultimate goal of comparative medical research is to deduce the results of animal experiments to humans, but applying the results of animal experiments to humans is by no means a simple inference or transplantation. This process requires iterative comparison and logic. Reasoning, and patient-centeredness is essential. Clinical Trials. Don't stop at a simple reasoning method, that is, simply infer from a small animal model to the human body. This type of extrapolation is taboo in scientific research and very dangerous, especially when applied to medical and pharmaceutical research. In short, the new animal disease model science is attracting experts from all disciplines to devote themselves to this development work. Even if medical scientists, veterinarians, and biologists want to replicate animal models, they need to learn relevant knowledge and be proficient in selecting various known models and developing new models. This is also a basic skill for researchers.