GENETIC ANALYSIS OF RETINAL DEGENERATION IN DROSOPHILA

大量的基因与遗传有关。 影响人类的视网膜变性综合征。 在 除了一个病例外，所有这些病例以及所有现有的动物模型中， 视网膜变性的基因产物的性质 不知道。 这项研究计划的长期目标是 了解参与的细胞和分子机制， 这些症状。 通过研究视网膜变性， 果蝇，优雅的遗传和分子 技术可以应用于这个问题。 该建议涉及两个分子的表征 与视网膜变性有关的基因 首先是 ninaE，由于其与脊椎动物视紫红质的同源性，我们可以 推断基因产物的三级结构。 体外 突变以及现有的DNA序列测定 突变体将限定特定肽区域的重要性， 这种蛋白质的功能。 第二个基因是rdgP 6。 rdgP6 突变在果蝇突变体中是独一无二的，并且可能被证明 是脊椎动物视网膜退行性疾病的良好模型。 没有 该基因的生理作用在变性中是明显的， 在老年果蝇中变得严重。 这里描述的实验 将检查rdgP 6基因和基因产物的性质。 这 基因将克隆利用最近分离的P-因子诱导 等位基因 DNA序列将被确定， 将寻找在脊椎动物视网膜中表达的同源基因。 我们将寻求遗传和环境条件， 增强或减弱rdgP 6视网膜变性的速率。 我们还将继续努力， 与视网膜变性有关的基因 这些变异的股票将 这对我们理解 视网膜变性过程中的分子事件。

A large number of genes have been implicated in the inherited retinal degeneration syndromes affecting human populations. In all but one of these cases, as well as in all existing animal models of retinal degeneration, the nature of the affected gene products is not known. The long term goal of this research program is to understand the cellular and molecular mechanisms involved in these syndromes. By investigating retinal degeneration in Drosophila melanogaster, elegant genetic and molecular techniques can be applied to this problem. This proposal concerns the molecular characterization of two genes involved in retinal degeneration. The first of these is ninaE, which due to its homology to vertebrate rhodopsins, we can infer the tertiary structure of the gene product. In-vitro mutagenesis as well as DNA sequence determination of existing mutants will delimit the importance of specific peptide regions to the function of this protein. The second gene is rdgP6. The rdgP6 mutation is unique among Drosophila mutants, and may prove to be a good model for vertebrate retinal degenerative diseases. No physiological effect of this gene is evident in degeneration that becomes severe in older flies. The experiments described here will examine the nature of the rdgP6 gene and gene product. This gene will be cloned by utilizing recently isolated P-factor induced alleles. The DNA sequence will be determined, and experiments will look for homologous genes expressed in the vertebrate retina. We will seek genetic and environmental conditions that either enhance or attenuate the rate of rdgP6 retinal degeneration. We will also continue our efforts to identify other Drosophila genes involved in retinal degeneration. These mutant stocks will allow an important contribution to our understanding of the molecular events involved in retinal degeneration processes.