A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision
A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision
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DOI：
10.1016/j.ydbio.2005.06.001
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发表时间：
2005-08-15
影响因子：
2.7
通讯作者：
Neuhauss, SCF
中科院分区：
文献类型：
--
作者：
Schonthaler, HB;Lampert, JM;Neuhauss, SCF
正向遗传筛选有助于定义视觉功能的分子组成部分。由于视力缺陷伴有视网膜色素上皮（RPE）和身体黑素细胞色素沉着不足，斑马鱼突变视力衰退（fdv）已在此类筛查中被鉴定出来。 RPE 形成视网膜的最外层，其功能对于视力至关重要。在 fdv 突变幼虫中，由于 RPE 细胞缺陷，光感受器外节的长度大大缩短或缺失。RPE 细胞的超微结构分析揭示了显着的细胞变化，例如微绒毛和囊泡内含物的缺失。根据生化分析判断，类维生素A谱发生了改变，认为部分阻碍了视色素再生。令人惊讶的是，纯合的 fdv 视力突变体能够存活到成年，并且尽管色素沉着不足持续存在，但视网膜形态部分恢复。通过定位克隆和随后的吗啉敲低，我们鉴定出银基因中的突变是 fdv 表型背后的分子缺陷。银蛋白是通过淀粉样裂解在黑素体中形成腔内原纤维所必需的。我们的数据揭示了黑素体生物发生和视觉系统之间的意想不到的联系，在细胞培养中无法检测到。 (c) 2005 Elsevier Inc. 保留所有权利。
Forward genetic screens have been instrumental in defining molecular components of visual function. The zebrafish mutant fading vision (fdv) has been identified in such a screen due to defects in vision accompanied by hypopigmentation in the retinal pigment epithelium (RPE) and body melanocytes. The RPE forms the outer most layer of the retina, and its function is essential for vision. In fdv mutant larvae, the outer segments of photoreceptors are strongly reduced in length or absent due to defects in RPE cells, Ultrastructural analysis of RPE cells reveals dramatic cellular changes such as an absence of microvilli and vesicular inclusions. The retinoid profile is altered as judged by biochemical analysis, arguing for a partial block in visual pigment regeneration. Surprisingly, homozygous fdv vision mutants survive to adulthood and show, despite a persistence of the hypopigmentation, a partial recovery of retinal morphology. By positional cloning and subsequent morpholino knock-down, we identified a mutation in the silver gene as the molecular defect underlying the fdv phenotype. The Silver protein is required for intralumenal fibril formation in melanosomes by amylogenic cleavage. Our data reveal an unexpected link between melanosome biogenesis and the visual system, undetectable in cell culture. (c) 2005 Elsevier Inc. All rights reserved.