RNA-sequencing of brain RNA from mice with compound mutations in ADAR1 and MAVS or ZBP1

The purpose of this study was to examine the role of MAVS and ZBP1 in the phenotype that develops when ADAR1 activity is missing, in particular when the Za domain of ADAR1 is mutated. Mice homozygous for a Za domain-mutant allele of Adar1 (Adar1mZa/mZa mice) were compared with control mice carrying one mZa allele and one wild type allele of Adar1 (Adar1wt/mZa mice) and with mice carrying one mZa and one null Adar1 allele (Adar1-/mZa mice). Adar1-/mZa mice were also compared with mice additionally deficient in ZBP1 (Adar1-/mZa Zbp1-/- mice) or MAVS (Adar1-/mZa Mavs-/- mice). Given the early postnatal lethal phenotype that develops in Adar1-/mZa mice, comparisons were made in RNA isolated from brain tissue from newborn mice of each genotype (4 mice per genotype).本研究旨在探究MAVS（线粒体抗病毒信号蛋白）与ZBP1（Z-DNA结合蛋白1）在ADAR1（RNA腺苷脱氨酶1）活性缺失，尤其是其Za结构域发生突变时所诱导产生的表型中的作用。我们将携带Adar1的Za结构域突变等位基因的纯合小鼠（Adar1^mZa/mZa小鼠）与两类对照小鼠进行比较：一类为携带1个mZa等位基因与1个野生型Adar1等位基因的对照小鼠（Adar1^wt/mZa小鼠），另一类为携带1个mZa等位基因与1个Adar1无效等位基因的小鼠（Adar1^-/mZa小鼠）。此外，我们还将Adar1^-/mZa小鼠分别与同时缺失ZBP1的小鼠（Adar1^-/mZa Zbp1^-/-小鼠）或缺失MAVS的小鼠（Adar1^-/mZa Mavs^-/-小鼠）进行对比。鉴于Adar1^-/mZa小鼠会出现出生后早期致死的表型，我们对各基因型新生小鼠脑组织中提取的RNA开展了比较分析，每个基因型使用4只小鼠。