ATM kinase inhibition in glial cells activates the innate immune response and causes neurodegeneration in Drosophila. Drosophila melanogaster

Analysis of the effects of ATM loss on gene expression to identify causes of neurodegeneration. ATM levels were reduced ubiquitously via the temperature-sensitive ATM^8 allele, or via tissue-specific RNAi of ATM (ATMi) using the Gal4/UAS expression system in neurons (Elav-GAL4 and ElavC155-GAL4) or glial cells (Repo-GAL4). Overall design: A 20-chip study using total RNA representing 2 replicates of 3 control genotypes (ATM^8/+, Repo-GAL4, and ElavC155-GAL4) and 3 experimental genotypes (ATM^8/ATM^8, Repo-ATMi, ElavC155-ATMi), and 4 replicates each of a control (Elav-GAL4) and experimental (Elav-ATMi) genotype

本研究通过分析共济失调毛细血管扩张症突变基因（Ataxia Telangiectasia Mutated, ATM）缺失对基因表达的调控效应，以鉴定神经退行性变的致病诱因。可通过两种策略降低ATM的表达水平：其一为利用温度敏感型ATM^8等位基因（temperature-sensitive ATM^8 allele）实现遍在性敲低；其二则借助Gal4/UAS表达系统（Gal4/UAS expression system），在神经元（Elav-GAL4与ElavC155-GAL4）或神经胶质细胞（Repo-GAL4）中介导ATM的组织特异性RNA干扰（RNAi of ATM，简称ATMi）。实验整体设计如下：本研究开展基于20张基因芯片的转录组分析，所用总RNA样本包括：3种对照基因型（ATM^8/+、Repo-GAL4及ElavC155-GAL4）与3种实验基因型（ATM^8/ATM^8、Repo-ATMi及ElavC155-ATMi），各设置2次生物学重复；此外，1种对照基因型（Elav-GAL4）与1种实验基因型（Elav-ATMi）各设置4次生物学重复。