GENETIC ANALYSIS OF RETINAL DEGENERATION IN DROSOPHILA

大量的基因被认为与遗传有关。 影响人类群体的视网膜变性综合征。在……里面 除一例外，所有这些病例以及所有现有的动物模型 视网膜变性，受影响基因产物的性质 是未知的。这项研究计划的长期目标是 了解细胞和分子机制涉及的 这些症状。通过研究视网膜退行性变 黑腹果蝇，优雅的遗传和分子 技术可以用来解决这个问题。 这项提议涉及两个分子的特征 与视网膜退化有关的基因。其中第一个是 由于它与脊椎动物视紫红质同源，我们可以 推测基因产物的三级结构。体外培养 现有细菌的诱变及DNA序列测定 突变体将特定多肽区域的重要性界定为 这种蛋白质的功能。第二个基因是rdgP6。RDGP6 突变在果蝇突变体中是独一无二的，并可能被证明 是脊椎动物视网膜退行性疾病的良好模型。不是 该基因在退行性变中的生理作用明显 在年龄较大的苍蝇身上变得严重。这里描述的实验 将检测rdgP6基因和基因产物的性质。这 利用新近分离的P-因子诱导克隆基因 等位基因。DNA序列将被确定，并进行实验 将寻找在脊椎动物视网膜中表达的同源基因。 我们将寻求符合以下条件的遗传和环境条件 增强或减弱rdgP6视网膜退行性变的速度。 我们还将继续努力识别其他果蝇 与视网膜退化有关的基因。这些突变种群将 允许对我们理解 参与视网膜变性过程的分子事件。

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.