动物造模,自发性疾病动物模型 中国实验动物信息网 2022-01-15 1412

　　Spontaneous animal models (spontaneous animal models) refer to experimental animals without any artificial treatment, in which experimental animals develop under natural conditions or are preserved through genetic breeding without artificial treatment due to abnormal performance of gene mutations. Spontaneous animal models are mainly tumors and genetic diseases, which can be divided into metabolic diseases, molecular diseases and special protein synthesis diseases. For example, spontaneously hypertensive rats, spontaneously diabetic 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, rats, spleen-deficient mice, immunodeficiency syndrome animals, etc. There are certain differences between the challenge model and the spontaneous disease model (for example, induced tumors and spontaneous tumors are The sensitivity of drugs is different), and some man-made diseases cannot be induced in animals by artificial methods, so they have attracted widespread attention. Last few years. Some scholars have conducted extensive research on the diseases of cats and dogs to find cases of spontaneous diseases. Since then, the model of this spontaneous disease has been maintained through genetic breeding. This is a biomedical research model that can be used in specific genetic conditions. Cultivate the characteristic mutant strains.

　　1. Examples of commonly used spontaneous animal models

　　Currently, the most commonly used spontaneous animal models in biomedical research are diabetes models, mainly rodents, ob, including/ob mice, db/db mice and KK mice. , NZO mice, NSY mice, fa/fa mice, OLETF mice, GK (Gotosaki) mice, SDT mice, etc.

　　Currently, there are about 250 million people with diabetes in the world, and it is estimated that by 2025, this number will reach 380 million. Between 2010 and 2030, the number of adult diabetic patients in developing countries increased by 69%, and the number of adult diabetic patients in developed countries increased by 69% to 20%, which is related to the diagnosis and treatment of diabetes. Research has attracted people's attention. Many animal models of spontaneous diabetes provide valuable "materials" for studying the development of human vascular diseases and finding treatment options. The ob/ob mouse is derived from C57BL/6J/ola and has the ob gene (obesity). This gene is a recessive gene on chromosome 6. The mice are sterile, simple obesity without diabetes, and obese mice weigh up to 60 grams. Homozygotes can be recognized within about 4 weeks, at which time weight gain accelerates and can quickly reach three times the normal litter weight. Moderate overeating can almost reduce activity, but blood sugar and immunologically active insulin did not increase significantly when young. After 5-6 months of age, obesity stabilizes, and insulin and glucose levels increase. These mice are not. Despite the influence of foreign insulin, diet can increase insulin sensitivity and extend its life. All female mice are non-parturient, with atrophy of ovaries and uterus. If proper eating habits are followed, male mice will occasionally breed. Obesity in ob/ob mice is very similar to human obesity. This type of mouse can be used to study the biochemistry, pathology, hormonal and drug treatments of human obesity. The mouse is infertile and must be mated with heterozygotes to maintain the gene. In addition to the ob mutant, ad mice were later discovered, namely adult obesity and diabetes (adult obesity and diabetes). The body weight of ad/ad obesity is twice that of normal mice. Like ob/ob obesity, obesity is usually infertility, with hyperglycemia and diabetes occurring within 7-10 weeks.

　　Db/db mouse (db/dbmouse) is a type 2 diabetes model derived from C57BL/KsJ inbreds with autosomal recessive inheritance. The animals started eating when they were one month old and gained weight. After that, it will produce hyperglycemia and high blood insulin, and glucagon will also 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. Four to five days before the onset of diabetic symptoms, pancreatic islets with obvious lymphocytic infiltration can be seen. 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, polydipsia, polyuria, obesity, hyperglycemia, hyperlipidemia, proteinuria. As the disease progresses, OLETF rats gradually develop renal mesangial matrix hyperplasia, glomerular basement membrane thickening, glomerular vitreous degeneration and nodular glomerulosclerosis, which are very similar to advanced humans. OD/LtJ mice are non-obese diabetic (NOD) mice. In the sixth generation of inbred reproduction of ICR/Jcl mice, non-obese diabetic and non-obese normal (NON) strains were isolated from sub-strains prone to cataracts. In the 20th generation of inbred lines, it was discovered for the first time that NOD female mice had insulin-dependent diabetes mellitus. From 90 to 120 days (equivalent to human puberty), ketonuria, diabetes, hyperglycemia, high cholesterol, polydipsia, polyuria, and bulimia nervosa occur. 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 spontaneously mutated 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 rise in blood glucose levels, loss of islet cells, and 10-month life span. The breeding of natural disease animal models 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 the mutations. Finally, we obtained the Chinese hamster with albinism, which is the source of the characteristics of albinism. Single gene mutation on chromosome 6.6. This hamster strain is an ideal laboratory animal for radiogenetics and cytogenetics research, and it is also the preferred model animal for Karaazar and amoebic liver abscess. Alzheimer's disease (AD) is a progressive dementia caused by degeneration of the nervous system, and the incidence of senile dementia is very high, also known as senile dementia. Experimental animals commonly used to study AD include non-human primates and rodents, and older rats older than 18 months have impaired learning and memory abilities. Neurons in the septal area, basal ganglia and oblique area nuclei. In the brains of rodent monkeys over 20 years old, the expression of ApoE and β-amyloid precursor protein increase with age, and correspondingly in amyloid plaques Increased antibodies. The staining of the disease has also increased. When Japanese scholars selected mice with natural AKR mutations and successfully inbred, they chose aging-promoting (SAMP) mice. SAMP has 9 sub-rows, among which SAMP8 is recognized as the aging model of AD. Compared with normal mice, SAMP8 mice have a shorter lifespan, a faster onset of brain deposits, and a higher incidence. After about 5 months of growth, the SAMP8 model experiences learning and memory loss, and may cause pathological changes, such as neuron depletion, neuron atrophy, and abnormal neurotransmitter metabolism. The SAMP8 model not only has the characteristics of naturally aging mice, but also has similar pathological changes in the learning and memory loss of the brain and Alzheimer's disease, which can better simulate the pathology of AD.