Rift Valley fever (RVF) is an emerging viral zoonosis that primarily affects ruminants and humans. We have previously shown that wild-derived MBT/Pas mice are highly susceptible to RVF virus and that part of this phenotype is controlled by a locus located on distal Chromosome 11. Using congenic strains, we narrowed down the critical interval to a 530 kb region containing five protein-coding genes among which Rnf213 emerged as a potential candidate. We generated Rnf213-deficient mice by CRISPR/CAS9 on the C57BL/6 J background and showed that they were significantly more susceptible to RVF than control mice, with an average survival time post-infection reduced from 7 to 4 days. The human RNF213 gene had been associated with the cerebrovascular Moyamoya disease (MMD or MYMY) but the inactivation of this gene in the mouse resulted only in mild anomalies of the neovascularization. This study provides the first evidence that the Rnf213 gene may also impact the resistance to infectious diseases such as RVF.

裂谷热 (RVF) 是一种新出现的病毒性人畜共患病，主要影响反刍动物和人类。我们之前已经表明野生来源的 MBT/Pas 小鼠对 RVF 病毒高度敏感，并且该表型的一部分由位于远端 11 号染色体的基因座控制。使用同类菌株，我们将临界间隔缩小到 530 kb 区域包含五个蛋白质编码基因，其中Rnf213成为潜在的候选基因。我们在 C57BL/6 J 背景下通过 CRISPR/CAS9产生了Rnf213 缺陷小鼠，结果表明它们比对照小鼠对 RVF 明显更敏感，感染后的平均存活时间从 7 天减少到 4 天。人类RNF213基因与脑血管烟雾病（MMD 或 MYMY）有关，但该基因在小鼠中的失活仅导致新生血管的轻度异常。这项研究提供了第一个证据，证明Rnf213基因也可能影响对 RVF 等传染病的抵抗力。