GENETIC ANALYSIS OF RETINAL DEGENERATION IN DROSOPHILA

特定的基因缺陷导致多种视网膜病变 影响人类人口的退化性疾病。这样做的目的是 研究计划是描述无脊椎动物的类似缺陷 黑腹果蝇。在果蝇中，有可能将 分子、遗传学、生理学技术以更好地了解 这些疾病背后的细胞活动的改变。 许多果蝇突变体以前是通过它们对 视觉传导过程也显示出光感受器的缺陷 维修。视觉色素视紫红质基因编码突变的研究 显示形成微绒毛的微绒毛膜的年龄相关性丢失 光感受器的横纹肌。一大批已定义的突变体样本 视紫红质蛋白已经产生：这些可能会影响 蛋白质的稳定性，蛋白质被糖基化的潜力， 或者蛋白质在膜上的位置。免疫组织化学 方法将研究这些视紫红质突变体的机制 影响横纹肌层结构。这些突变的视紫红质中的每一个也将是- 在体外系统中表达，以研究其内在稳定性和 修饰的视紫红质蛋白的视网膜结合能力。 一种新发现的基因，丙二醛，在结构和 光感受器的功能。该基因中的突变体存在缺陷 视觉传导，也显示微绒毛结构紊乱。 横纹肌的细胞质表面。这一区域是亚细胞站点 横纹体膜的更新以及可能的分子位置 光传导反应的基础事件。分子 该基因的特征将解决编码基因的作用 产品在感光器的维护和功能上。 RdgC具有类似于遗传性视网膜的突变表型 影响人类人口的退化综合症。也就是说，没有 视网膜发病前明显的视觉过程缺陷 退化。光刺激视紫红质触发rdgC变性 变种人。因此，rdgC基因产物起到预防视网膜的作用。 由于正常的视紫红质活动而导致的变性 直接参与光传导途径。演绎法线 RdgC蛋白在光感受器中的功能，我们将使用分子 鉴定rdgC基因和基因产物的技术。遗传 策略将用于确定在以下方面发挥作用的其他组件 与rdgC协调以维持感光器结构。

Specific genetic defects are responsible for a variety of retinal degeneration diseases that affect human populations. The goal of this research program is to characterize analogous defects in the invertebrate Drosophila melanogaster. In Drosophila, it is possible to combine molecular, genetic, physiological techniques to gain a better understanding of the altered cellular activities that underlie these diseases. Many Drosophila mutants previously identified by their effects on the process of visual transduction also show defects in photoreceptor maintenance. Mutants in the gene coding for the visual pigment rhodopsin show an age dependent loss of the microvillar membranes that form the rhabdomere of the photoreceptors. A large sample of defined mutants in the rhodopsin protein have been generated: these are likely to affect the stability of the protein, the potential of the protein to be glycosylated, or the positioning of the protein in the membrane. An immunohistochemical approach will investigate the mechanisms by which these rhodopsin mutants affect rhabdomere structure. Each of these mutant rhodopsins also will be - expressed in an in-vitro system to investigate the inherent stability and retinal binding capacity of the modified rhodopsin proteins. A newly identified gene, mda, plays a critical role in the structure and function of the photoreceptors. Mutants in this gene are defective in visual transduction and also show disarranged microvillar structures on the cytoplasmic face of the rhabdomeres. This region is the subcellular site of rhabdomeric membrane renewal and also likely the location of molecular events underlying the phototransduction response. Molecular characterization of this gene will address the role of the encoded gene product in photoreceptor maintenance and function. rdgC has a mutant phenotype that is similar to the inherited retinal degeneration syndromes that affect human populations. That is, there is no obvious defect in visual processes before the onset of retinal degeneration. Light stimulation of rhodopsin triggers degeneration in rdgC mutants. Therefore, the rdgC gene product acts to prevent retinal degeneration that occurs as a consequence of normal rhodopsin activity not directly involved in the phototransduction pathway. To deduce the normal function of the rdgC protein in photoreceptors, we will use molecular techniques to characterize the rdgC gene and gene product. Genetic strategies will be used to identify additional components that act in concert with rdgC to maintain photoreceptor structure.