疾病动物模型,诱发视网膜色素变性动物模型 z-bio 2021-12-27 271

　　Drugs or physical methods that induce retinal diseases are used to change the structure of the retina, resulting in diseases similar to human retinitis pigmentosa. The operation of the animal model of RP disease induced by physical and chemical factors is simpler than that of the genetically modified RP model, and the effect is more obvious. This article introduces the commonly used animal models of N-ethyl-N-nitrosourea (ENU)-induced RP disease. [Modeling mechanism] ENU is a powerful mutagen, which can move ethane groups to the oxygen or nitrogen atoms of DNA bases, regardless of the metabolic process. Point mutations in DNA are more common and can cause genetic abnormalities in the retina and optic disc. It can mutate genes such as Pde6b, Roml, Pax6, Mitf and Egr, causing eye and vision problems. Hart et al. They used ENU in mice and discovered seven new Pde6b point mutations that cause the death of photoreceptor cells. ENU induces Rom1 gene mutations, disrupts the outer segmental intervertebral disc membranes and degenerates photoreceptor cells.

　　[Modeling method] The RP model guided by ENU has excellent repeatability. Currently, C57BL/6J and BALB/cAnN mice are often used for modeling. C57BL/6J male mice were selected for 8-10 weeks, and 85-100mg/kg ENU was injected intraperitoneally twice a week. After screening for eye diseases, retinitis pigmentosa mice and wild-type female mice were bred in a sterile environment to produce the first generation (F1) offspring. F1 generation male mice and wild-type female mice were mated, and F2 generation female mice and F1 generation male mice were backcrossed. The resulting F3 generation mice were used for large-scale eye screening to obtain hereditary retinitis pigments. Transgender animal model.

　　[Model Features] The Rom1 mutation of ENU was similar to the network structure of the control group at 3 weeks, and the outer nuclear layer was 1/3, or only one, of the outer nuclear layer of the control group at 7 weeks. Two floors. It was kept for 35 weeks. Through capillary electrophoresis and DNA sequencing, the Pde6b mutant mice induced by ENU were identified as Pde6b. From 25 days to 10 weeks of age, Pde6b mutant mice exhibit dynamic visual acuity. Almost all rod photoreceptor cells in Pde6b mutant mice died within 17 days.

　　[Model evaluation and application] ENU-induced eye diseases require fundus screening and visual function tests, as well as genome-wide screening to determine the genes that cause the disease. The ENU-induced RP animal model has a high incidence and good reproducibility, but it is difficult to predict the incidence of specific genes. The animal model of retinitis pigmentosa induced by ENU is an artificial method that can overcome the shortcomings of spontaneous retinal genetic diseases that may be encountered but not sought, and can simulate human genetic RP diseases.