Evaluation of the effect of antimiR-122 administration on the liver, spleen and heart miRNome

To determine the effect of antimiR-122 administration on the mouse miRNome. To functionally investigate a possible link between miR-122 and iron metabolism we inhibited miR-122 by a single, intraperitoneal injection of Locked Nucleic Acid (LNA)-modified antimiR oligonucleotides into age- and sex-matched C57Bl/6 WT mice. To inhibit miR-122 specifically, we injected an antimiR compound with perfect complementarity to miR-122 [perfect match (PM); PM_antimiR-122]. As negative controls, mice were either injected with an LNA control compound with two mismatches (2MM, 2MM_antimiR-122) or the vehicle control (SAL; 0.9% NaCl). Mice were sacrificed three and six weeks after injection. Independent of treatment, mice were viable and exhibited no overt physical or behavioral abnormalities. To exclude that PM_antimiR-122 administration disturbs the expression of other miRNAs we analyzed miRNA expression profiles in the livers, hearts and spleens of the same mice.

本研究旨在探究抗miR-122给药对小鼠miRNA组（miRNome）的影响。为从功能层面解析miR-122与铁代谢之间的潜在关联，我们通过单次腹腔注射锁核酸（Locked Nucleic Acid, LNA）修饰的抗miR-122寡核苷酸，对年龄与性别匹配的C57Bl/6野生型小鼠实施miR-122抑制。为实现对miR-122的特异性抑制，我们使用了与miR-122完全互补的抗miR-122化合物[完全匹配（perfect match, PM）组：PM_antimiR-122]。作为阴性对照，小鼠分别接受带有两个错配位点的LNA对照化合物（2MM组：2MM_antimiR-122）或溶剂对照（SAL组：0.9%氯化钠注射液，即生理盐水）。分别于给药后3周和6周处死所有小鼠。无论接受何种处理，所有小鼠均存活且未表现出明显的躯体或行为异常。为排除PM_antimiR-122给药对其他miRNA表达的干扰，我们对上述小鼠的肝脏、心脏及脾脏组织进行了miRNA表达谱分析。