疾病动物模型,白内障动物模型 z-bio 2021-03-12 503

　　Although in clinical practice, there are more presbyopia than congenital cataracts, most animal models of genetically engineered cataracts are congenital cataracts. In recent years, some scholars have applied these methods to zebrafish to improve the efficiency of screening models.

　　[Modeling mechanism] Cats, dogs, rabbits and other large and medium-sized animals can also be used as cataract animal models, but for the convenience of reproduction and reproduction, rats and mice are usually used. The commonly used mutagenic substance ENU is an alkylating agent, which is a carcinogen. It acts directly on DNA and mainly forms O6-ethylguanine, causing base mismatches. The target organs of its action vary greatly depending on the animal species and the route of administration. After ENU was injected intraperitoneally into mice, they caused mutations in many tissues, mainly the kidneys, spleen, and lungs.

　　[Modeling method] EUN phosphate solution was dissolved and injected into the abdominal cavity of mice at 160 mg/kg (pH 6.0, concentration 66 mM) and 250 mg/kg (pH 6.0, concentration 30 mM) within 10 to 17 weeks. ...After the injection, the male and female mice mate 2:1, after closing the cage, check the vaginal plug of the female mouse with tweezers. A vaginal plug was found on the 0th day of conception. Vaginal suppositories are milky white or light yellow suppositories and usually take 12-14 hours. Vaginal smears can also be used to check sperm, indicating that the sperm is a normal mating mouse. As a result, it matches the vaginal suppository method by 90% or higher, and when used in combination, the diagnostic accuracy can be improved. Male puppies (f1, F1) who became pregnant 42 days after intraperitoneal injection of drugs were selected for cataract screening. Based on this, the first generation of cataracts selected from mating female and male mice can be used to establish genetic cataract mouse models. A variety of transgenic cataracts obtained by using this method are reported, including lens membrane-related genes, lens protein-related genes, cytoskeleton protein genes, heat shock proteins, growth factor protein genes, etc. It can be classified. Used for location and function. Many genes and proteins are involved in the growth, development and maintenance of cataracts. Changes in the link can cause cataracts. Transgenic transgenic animals not only reveal related genes related to cataracts, but also help us understand their lens development and function maintenance more deeply. [Model characteristics] Because the cataract models obtained by induced mutations have different phenotypes, different ages of onset, and unclear genetic background, it is not yet certain.

　　[Model Evaluation and Application] Initially, people used chemicals and radiation to irradiate parents to obtain animal models of hereditary cataracts. The disadvantages are also obvious. In addition to heavy workload, poor controllability and reproducibility, tedious experiments are also required to verify the main mutation sites in the selected animals. Animals obtained at the same time are usually related to abnormal development of other organs. Recently, tissue-specific gene knockout has become possible, making a large number of transgenic animals easily available. The combination of molecular biology analysis of gene knockout and detailed animal phenotype analysis can better understand the processes and pathways of eye development. Some animals obtained by these methods develop cataracts later than senile cataracts, but different from the natural process of senile cataracts, these animals are either shortly after birth or in the embryonic stage, and there are changes before the occurrence of cataracts.