先天性静止性夜盲模型,疾病动物模型 z-bio 2021-12-27 413

　　Congenital stationary night blindness (CSNB) is a type of hereditary retinal disease, which manifests as visual disturbance in the dark and difficulty in movement, but the vision is better in a bright environment, and there is no abnormality in the field of vision and fundus. The dark adaptation function of this disease is reduced, the dark adaptation time is prolonged, and night blindness symptoms can appear after birth, which generally does not increase with age. With or without nystagmus, strabismus, and refractive errors, no fundus changes or no progression of fundus pathology, the main manifestations are the dysfunction of retinal rod cells.

　　[Modeling mechanism] The Peachey Laboratory of the Cole Eye Institute in the United States discovered in 1998 nob1 mice without electroretinogram (ERG) b waves and normal a waves. The pathogenic gene was determined to be NYX. Later, nob3 and nob4 were found. The pathogenic genes of mice are all Grm6 mutations. In 2006, Chang B et al. discovered a nob2 mouse with a visual electrical appearance similar to iCSNB, and the cacnalf gene was found. In 2002, Zhang Zuoming and others discovered and bred rats with similar human CSNB disease through visual electrical testing. The genetic characteristics of this CSNB rat are X-linked recessive inheritance, and the visual electrical phenotype is similar to that of cCSNB disease. In 2008, Gu reported that through molecular biology technology, the cacnalf gene was preliminarily verified, and through genetic typing, this type of CSNB model rat may belong to iCSNB disease.

　　[Model Features] In 2001, Krishna studied the ERG characteristics of different frequencies in nob1 mice. Studies have shown that under low frequency conditions, nob1 mice have significant differences in amplitude and waveform phase compared with normal mice. With the gradual increase in stimulation frequency, Ball uses immunohistochemical methods to prove that nob1 mice have The expression of mGluR6, PKC, GOalpha, bassoon, PSD-95, alpha1FVGCC, trkB, dystrophin and other protein expressions are indistinguishable from those in the retina of normal control mice. It is believed that nyctalopin mutation affects synaptic transmitter transmission, but the specific protein affected is also Not sure. Chang B et al. used electrophysiology to detect the visual response of ganglion cells in nob2 mice and found that the dynamic range of ON-center cells was reduced under light adaptation, while the response of OFF-center cells was not abnormal. Yu and Peachey et al. found in nob2 mouse oscillatory potential experiments that OPs under low-frequency stimulation have lower amplitudes. Although Cav1.4 is expressed in both the inner and outer reticulum layers, the lesions are mainly located in the outer reticulum layer. Bayley (2007) also reported abnormal positions of rods and horizontal cell dendrites in the outer mesh layer of nob2 mice, and ectopic synapses were formed at the tops of the dendrites.

　　CSNB rat visual electrophysiological results showed that the scotopic function was severely damaged, and the photopic function was also affected. Cacnalf mutation affects the development and maturation of horizontal cells, and significantly reduces the nerve fiber connections between bare rod cells and horizontal cells. In addition, the outer reticulum layer of CSNB rats became thinner, and the number of synaptic link Ribbon bodies in the outer reticulum layer decreased.

　　[Model evaluation and application] Four types of nob mice and one type of CSNB rat have been found. They all have a typical visual electrophysiological phenotype similar to human CSNB disease, and corresponding changes in the retinal structure hinder visual signals. Conduction from the primary neurons of the retina to secondary neurons. These animal models of CSNB disease provide a theoretical basis for the in-depth study of the pathogenesis of CSNB disease and the expansion of treatment methods.