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    • 9. 发明申请
    • NEURONAL AND RETINAL GENE EXPRESSION PATTERNS
    • 神经元和视网膜基因表达模式
    • WO2004007674A3
    • 2004-10-07
    • PCT/US0321737
    • 2003-07-14
    • UNIV JOHNS HOPKINSZACK DONALD JHACKAM ABIGAIL SHOSHANNA
    • ZACK DONALD JHACKAM ABIGAIL SHOSHANNA
    • A61K38/00C07K14/47C12N5/08C12Q1/68A61K39/00A61K39/395C07K16/00C07K16/18C07K16/22C07K16/24
    • C12Q1/6883A61K38/00A61K2039/505C07K14/47C12Q1/6837C12Q2600/158
    • The retinal degeneration (rdl) mutant mouse exhibits rapid rod photoreceptor degeneration caused by a mutation in the rod photoreceptor-specific gene cGMP phosphodiesterase beta (PDE). One intriguing aspect of the rdl phenotype is a secondary wave of cone photoreceptor death that follows loss of rods. In this study, we investigated gene expression changes associated with the progression of photoreceptor degeneration in rdl mice using a custom retina microarray. The microarray contains 5,376 DNA fragments that correspond to mouse genes known or postulated to be involved in normal retinal function, development, or disease. Gene expression in rdl retina was compared with age-matched wild-type controls at three time-points corresponding to critical stages in retina degeneration: peak of rod degeneration, early in cone degeneration and during cone degeneration. Statistical significance analyses demonstrated that approximately 3% of the genes on the microarray were differentially expressed, including known genes and genes that had not been previously implicated in degeneration. Interestingly, there was less overlap in the genes that were upregulated at each stage of degeneration, suggesting the involvement of distinct molecular pathways. Genes involved in transport, signalling and cytoskeleton were differentially expressed during rod degeneration whereas genes involved in growth and proliferation, oxidative stress and protein modification were increased prior to and during cone degeneration. These results provide clues to underlying molecular processes occurring during photoreceptor degeneration, and provide direction for future cell-based studies.
    • 视网膜变性(rdl)突变小鼠表现出由杆状光感受器特异性基因cGMP磷酸二酯酶β(PDE)中的突变引起的快速视杆光感受器变性。 rdl表型的一个有趣的方面是锥形光感受器死亡的次级波,其在棒损失之后。 在这项研究中,我们使用定制视网膜微阵列研究了rdl小鼠中与光感受器变性进展相关的基因表达变化。 微阵列含有5,376个DNA片段,其对应于已知或假定参与正常视网膜功能,发育或疾病的小鼠基因。 将rdl视网膜中的基因表达与年龄匹配的野生型对照在对应于视网膜变性关键阶段的三个时间点进行比较:棒状变性的峰值,锥状变性早期和锥状变性期间。 统计学显着性分析表明,微阵列上约3%的基因是差异表达的,包括已知的基因和先前未涉及退化的基因。 有趣的是,在每个退化阶段上调的基因重叠较少,这表明不同分子途径的参与。 涉及运输,信号传导和细胞骨架的基因在杆变性过程中差异表达,而参与生长和增殖,氧化应激和蛋白质修饰的基因在锥变性之前和期间增加。 这些结果为光感受器退化过程中发生的潜在分子过程提供了线索,并为未来基于细胞的研究提供了方向。