动物模型 z-bo 2022-02-06 396

　　[Modeling mechanism] 1. KK-Ay mouse obesity model Ay is a mouse strain based on the Agouti(A) gene mutation of the KK mouse strain. Ay gene is widely expressed in KK mice. Ay protein is considered to be an antagonist of melanocortin 4 receptor (melanocortin 4 receptor), thus inhibiting the stimulation of hormone signals by melanocytes and affecting the regulation of energy balance.

　　[Model Features] KK-Ay mice weigh about 45 g when they are 2 months old and can be considered a model of moderate obesity. The weight of four to five months old mice is basically stable. About 50-60g, of which adipose tissue accounts for about 33% of total body weight. Please also note that this mouse strain is related to diabetes. [Assessment of model and application range] The obesity and diabetes onset of KK-Ay mice is similar to that of humans, and is widely used in non-clinical drug research.

　　2. Obesity model of ob/ob and db/db mice after C57BL/6J [modeling mechanism] ob/ob mouse (ob/obmouse) is the key point of leptin gene, which can cause leptin signal transduction pathway to be affected. damage. It is caused by mutations and cannot be produced in the body. Caused by leptin. In 1949, the mouse was found in the Jackson Laboratory of the United States and then returned to the C57BL/6J background. The db/db mouse (db/dbmouse) is an obesity model caused by a point mutation in the leptin receptor gene, which leads to the leptin signaling pathway. Currently, the most commonly used are the C57BL/6J background strains of ob/ob and db/db mice.

　　3. Zucker rat obesity model [Modeling mechanism] is an obesity model caused by an autosomal recessive mutation in the fat gene (fa) discovered by Zucker in 1961. Due to the lack of leptin receptor function, fa/fa homozygosity leads to obesity.

　　[Characteristics of the model] Ob/ob mice and db/db mice can show obesity phenotype at 4 weeks of age, and obvious obesity at 8 weeks of age. Please note that C57BL/6J background ob/ob mice exhibit a transient diabetic phenotype at 14-16 weeks of age. The db/db mouse behind C57BL/6J has similar properties. [Evaluation and application range of the model] ob/ob mice are widely used, and are now commonly used in obesity models or diabetes models. There are many similarities between the db/db mouse strain and the ob/ob mouse strain, but the phenotypes of different backgrounds are inconsistent, and should be selected according to the experimental purpose.

　　[Characteristics of the model] It was found that Zuckerobeserat had a strong appetite and low energy expenditure, and revealed an obesity model. Lipids are preferentially deposited in adipose tissue. When Zooker rats are 14 weeks old, the weight of fat accounts for 40% of body weight.

　　[Evaluation of model and application range] Zucker rats developed insulin resistance due to obesity, but their blood sugar levels were normal, and they had not yet developed into a clear diabetes model. It is very similar to human obesity, showing both obesity and insulin resistance, but not diabetes. Therefore, Zucker rats are considered to be more suitable models for metabolic diseases (such as obesity).