动物模型 z-bo 2020-08-03 591

　　nduction of retinal diseases, drugs or physical methods are used to change the structure of the retina, resulting in a disease similar to human retinitis pigmentosa. The operation of the animal model of RP disease induced by physical and chemical factors is easier and more obvious than the operation of the transgenic RP model. In this article, we introduce the common animal models of RP disease induced by N-ethyl-N-nitrosourea (ENU).

　　[Modeling mechanism] ENU is a powerful mutagen, and ENU can transfer ethylene to the oxygen or nitrogen atoms of DNA bases without relying on metabolic processes. The frequency of point mutations in DNA is very high and can cause genetic abnormalities in the retina and optic nerve head. It can induce mutations in genes such as Pde6b, Roml, Pax6, Mitf, and Egr, leading to abnormal eyes and vision. Hart et al. used ENU in mice to discover seven new Pde6b point mutations that can cause photoreceptor cell death. ENU induced a mutation in the Rom1 gene, which disrupted the degeneration of the outer segmental disc membrane and photoreceptor cells.

　　[Modeling method] The ENU-induced RP model has good 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 every week. After screening for eye diseases, retinitis pigmentosa mice and wild-type female mice were mated in a sterile environment to produce the first generation (F1) offspring. F1 male mice and wild-type female mice were crossed, F2 female mice and F1 male mice were backcrossed, and the resulting F3 mice were used for large-scale ophthalmological screening to obtain hereditary retinitis pigments. Transgender animal model. [Characteristics of the model] The Rom1 mutation induced by ENU was similar to the retinal structure of the control group at 3 weeks, and at 7 weeks, the outer nuclear layer was 1/3 of the control group. Within a week, the outer nuclear layer was only There are 1-2 layers left. .. The Pde6b mutant mice induced by ENU were identified as Pde6b by capillary electrophoresis and DNA sequencing. The dynamic vision of Pde6b mutant mice after birth is 25 to 10 weeks. Almost all rod photoreceptor cells in Pde6b mutant mice died on the 17th day. [Model evaluation and application] In addition to fundus screening and visual function tests, ENU-induced ophthalmic diseases also require genome-wide screening to determine virulence genes. Although ENU-induced RP animal models have a high incidence and reproducibility, it is difficult to predict the incidence of specific genes. The animal model of ENU-induced hereditary retinitis pigmentosa overcomes the potential shortcomings of naturally occurring retinal genetic diseases and provides an artificial method to simulate human genetic RP diseases.