动物造模,自发性疾病动物模型 z-bo 2021-01-07 317

　　Spontaneous disease animal models, animal models that occur under natural conditions, or animal models that are preserved through genetic breeding without artificial treatment due to abnormal expression of gene mutations. Spontaneous animal models are mainly tumors and genetic diseases, which can be divided into metabolic diseases, molecular diseases and special abnormal protein synthesis. For example, spontaneously hypertensive rats, spontaneously diabetic Chinese hamsters, various spontaneous tumor mice and rats, obese mice, stroke rats, diabetic rats, diabetic mice, epileptic animals, hereditary hypertension Rats, glaucoma rabbits, nude mice, nude mice, mice with insufficient spleen, and animals with immunodeficiency syndrome have certain differences between the stimulation model and the spontaneous disease model (for example, induced and spontaneous tumors versus drugs The sensitivity is different), and some man-made diseases cannot be induced in animals by artificial methods. Therefore, in recent years, people have paid great attention to the development of animal models of spontaneous diseases. Some scholars have conducted extensive research on diseases of cats and dogs to find cases of spontaneous diseases and then conduct genetic research. We carry out this naturally occurring disease through reproduction. The model can be maintained and cultivated in mutant strains with specific genetic characteristics, thereby providing a model for biomedical research.

　　 1. Examples of some commonly used spontaneous animal models

　　 At present, the most commonly used animal models of spontaneous diseases in biomedical research are diabetes models, mainly rodents. Types include ob/ob mouse, db/. db mouse, KK mouse, NZO mouse, NSY mouse, fa/fa mouse, OLETF mouse, GK (Goto Kakizaki) mouse, SDT mouse.

　　 Currently, it is estimated that there are about 250 million diabetic patients in the world, which will reach 380 million by 2025, and it will develop between 2010 and 2030. The number of adult diabetic patients in the country will increase by 69%, while the number of adult diabetic patients in developed countries will increase. Since this ratio reaches 20%, research on the diagnosis and treatment of diabetes has attracted attention. Many animal models of spontaneous diabetes provide valuable "materials" for studying the development of human vascular diseases and finding treatment options. ob/ob mice are derived from C57BL/6J/ola and have ob gene (obesity). This gene is a recessive gene on chromosome 6. This type of mouse has no fertility, but is obese without diabetes. Obese mice weigh up to 60 grams. Homogeneous knots can be recognized after about 4 weeks, at which time weight gain accelerates and can quickly reach three times the weight of ordinary garbage. Moderate overeating is almost inactive, but blood sugar and immune-active insulin will not increase significantly when you are young. After 5-6 months of age, obesity stabilizes and insulin and glucose levels increase. These mice are not affected. Due to the role of external insulin, diet can increase sensitivity to insulin and extend its life. All female mice are sterile and have atrophy of ovaries and uterus. With a moderate diet, male mice may breed. Ob/ob mouse obesity is very similar to human obesity and can be used to study the biochemistry, pathology, hormone and drug treatment of human obesity. The mouse is infertile and must be mated with heterozygotes to maintain the gene. In addition to ob variants, ad mice were later discovered, namely adult obesity and diabetes (adult obesity and diabetes). The weight of ad/ad obese people is twice that of normal mice. Like ob/ob type, obesity is usually infertile, accompanied by high blood sugar and diabetes, lasting 7-10 weeks.

　　 Db/db mouse (db/dbmouse) is a type 2 diabetes model derived from the C57BL/KsJ non-related line with autosomal recessive inheritance. These animals started eating when they were one month old and began to get fat. After that, it will produce high blood sugar and high insulin, and glucagon will increase. They usually die within 10 months. Another background diabetic mouse (C57B/6Jdb/db) showed severe diabetic symptoms similar to C57B/KsJob/ob mice: early onset of hyperinsulinemia, weight loss and early death. Unlike ob/ob mice, db/db mice can develop obvious kidney disease. LETL (Long-Evans Tukushimalean) rat is an animal model of type 1 diabetes. Diabetes usually develops within 8 to 20 weeks. Pancreatic islets with obvious lymphocyte infiltration can be seen 4-5 days before the onset of diabetic symptoms. OLETF (Otsuka-Long. Evans Tokushimafatty) rats are spontaneous type 2 diabetes animal models established by Long-Evans rats. This model is characterized by type 2 diabetes. Polyphagia, hyperlipidemia, polyuric acid, obesity, hyperglycemia, hyperlipidemia, proteinuria. As the disease progresses, OLETF rats gradually develop glomerular membrane matrix hyperplasia, glomerular basement membrane thickening, glomerular vitreous degeneration and advanced nodular glomerulosclerosis, which are very similar to humans. OD/LtJ mice are non-obese (NOD) mice. In the sixth-generation allogeneic mating of ICR/Jcl mice, non-obese diabetic strains and non-obese normal strains (NON) were isolated from sub-strains prone to cataracts. In the 20th generation of close, NOD female mice, insulin-dependent diabetes mellitus was discovered for the first time. From 90 to 120 days (equivalent to human puberty), ketonuria, diabetes, hyperglycemia, hypercholesterolemia, gypsy, polyuria and sulphurosis will appear. The clinical symptoms are similar to human type 1 diabetes. Diabetic obese mice (BKS.Cg.Doek7m +/+ Leprdb/Nju) are derived from C57BLKS/Nju mice and are formed by defects in the Leprdb gene. Homozygous spontaneous mutation C57BLKS/Nju mice develop a recognizable obese phenotype within 3-4 weeks. Plasma insulin and blood sugar levels begin to rise 10-14 days after birth. Many characteristics were observed: uncontrolled increase in blood glucose levels, loss of islet cells and 10-month life span. The reproduction of animal models of natural diseases can also be obtained through breeding and mating methods. Albino Chinese Hamster (A: CHA) is a researcher who discovered albino mutations in the breeding population of Chinese hamsters, followed and selected these mutations, and finally obtained albino Chinese hamsters, which are the source of the albino traits. A single gene mutation on chromosome 6. This hamster strain is an ideal laboratory animal for radiological and cytogenetic research, and is the preferred model animal for Karaazar and amoeba liver abscess. Alzheimer's disease (AD) is a progressive dementia caused by the degeneration of the nervous system, and has a high incidence of senile disease, also known as senile dementia. Experimental animals commonly used to study AD include non-human primates and rodents. Aged rats older than 18 months have decreased learning and memory abilities. Neurons in the septal area, basal nucleus and oblique nucleus were significantly atrophied; senile plaques appeared in the brain of cynomolgus monkeys over 20 years old. With age, the expression of ApoE and β-amyloid precursor protein increases, and the positive staining of corresponding antibodies in senile plaques also increases. When Japanese scholars breed and successfully mate mice with natural AKR mutations, they will choose anti-aging tendency (SAMP) mice. SAMP has 9 sub-lines, of which SAMP8 is widely regarded as an AD aging model. Compared with normal mice, SAMP8 mice have a shorter lifespan, the onset of brain deposition is faster, and the incidence is higher. After about 5 months of growth, the learning and memory of the SAMP8 model decrease, and may cause pathological changes, such as neuron loss, nerve cell atrophy, and abnormal neurotransmitter metabolism. .. SAMP8 model not only has the characteristics of naturally aging mice, but also has similar brain pathological changes and impaired learning and memory function of Alzheimer's disease, which can better simulate the pathology of AD.