Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae
Dystrophin and beta-dystroglycan in photoreceptor terminals from normal and mdx3Cv mouse retinae
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DOI：
10.1046/j.1460-9568.1999.00636.x
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发表时间：
1999-06-01
影响因子：
3.4
通讯作者：
Kröger, S
中科院分区：
文献类型：
--
作者：
Blank, M;Koulen, P;Kröger, S
抗肌萎缩蛋白基因的突变会导致肌肉萎缩症以及认知障碍，包括异常的暗适应视网膜电图。为了研究眼部表型的基础，我们分析了mdx(3Cv)小鼠视网膜中的抗肌萎缩蛋白以及抗肌萎缩蛋白相关蛋白β -肌聚糖。该品系在抗肌萎缩蛋白基因上存在突变，其视网膜电图异常与肌肉萎缩症患者相似。尽管突变小鼠视网膜组织中所有抗肌萎缩蛋白异构体以及β -肌聚糖总体减少，但我们观察到视网膜的组织学分层以及几种特定细胞类型（包括视杆细胞和视锥细胞）的超微结构没有明显变化。在野生型和mdx(3Cv)小鼠的视网膜中，抗肌萎缩蛋白和β -肌聚糖集中在视杆和视锥光感受器终末突入外网状层的小突起中。β -肌聚糖（而非抗肌萎缩蛋白）也聚集在内界膜和毛细血管基膜周围。虽然突变小鼠基膜周围的标记模式没有改变，但我们发现与视杆光感受器终末相关的抗肌萎缩蛋白和β -肌聚糖免疫反应性的区域以及强度都严重降低。相同参数在视锥细胞终末受影响要小得多。这些结果表明，抗肌萎缩蛋白和β -肌聚糖在视网膜中分布不同，抗肌萎缩蛋白的严重减少对视网膜结构没有显著影响，但可能会影响光感受器终末水平的视网膜内信号传导。此外，mdx(3Cv)小鼠的突变对视杆细胞有选择性影响，这为视网膜电图的改变提供了解释。
Mutations in the dystrophin gene cause muscular dystrophy as well as cognitive impairments, including an abnormal dark-adapted electroretinogram. To investigate the basis for the ocular phenotype, we analysed dystrophin and the dystrophin-associated protein beta-dystroglycan in retinae from mdx(3Cv) mice, This strain has a mutation in the dystrophin gene and abnormalities in the electroretinogram which are similar to those of muscular dystrophy patients. Despite an overall reduction of all dystrophin isoforms and of beta-dystroglycan in retinal tissue from mutant mice, we observed no apparent change in the histotypic layering of the retina, or in the ultrastructure of several specific cell types, including rods and cones. In retinae from wild type and mdx(3Cv) mice, dystrophin and beta-dystroglycan were concentrated in small extensions of rod and cone photoreceptor terminals protruding into the outer plexiform layer. Beta-dystroglycan but not dystrophin was also clustered around the inner limiting membrane and the capillary basal laminae. While the labelling pattern around the basal laminae was not altered in the mutant mice, we found that the area as well as the intensity of the dystrophin and beta-dystroglycan immunoreactivity associated with the terminals of rod photoreceptors were severely reduced. The same parameters were much less affected in cone terminals. These results show, that dystrophin and beta-dystroglycan are differentially distributed in the retina, and that a severe reduction of dystrophin has no gross effect on retinal structure, but could influence intraretinal signalling at the level of the photoreceptor terminals. Moreover, the mutation in mdx(3Cv) mice has a selective effect on rods, providing an explanation for the altered electroretinogram.