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The ring finger protein 213 gene (Rnf213) contributes to Rift Valley fever resistance in mice

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Abstract

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.

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Acknowledgements

We are grateful to all members of the laboratory for technical advice and helpful discussion. We are grateful to Lauranne Machou and María Bernad Roche for their precious help during their short stay in the laboratory. We would like to thank the members of the Mouse Genetics Engineering Center, Sébastien Chardenoux, Ilta Lafosse, and Gaëlle Chauveau Le Friec for technical support with transgenic mice. This work was supported by the Agence Nationale de la Recherche (Grant No. 11-BSV3-007 01, ‘GenRift’) and the French Government's Investissement d'Avenir program, Laboratoire d'Excellence Integrative Biology of Emerging Infectious Diseases (Grant No. ANR-10-LABX-62-IBEID).

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Contributions

DH conceived the study, performed the experiments, analyzed the data, and wrote the manuscript. DS-C performed in vivo experiments. LB and ST produced congenic strains. FLV and her team produced the Rnf213tm3 founder individuals. MF and her team assisted with RVFV production and titration. XM assisted with data analysis, performed in vivo experiments, and wrote the manuscript. J-JP provided funding, conceived the study, and wrote the manuscript.

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Correspondence to Denis Houzelstein.

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The authors declare that they have no conflict of interest.

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Xavier Montagutelli and Jean-Jacques Panthier have contributed equally to this work.

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Houzelstein, D., Simon-Chazottes, D., Batista, L. et al. The ring finger protein 213 gene (Rnf213) contributes to Rift Valley fever resistance in mice. Mamm Genome 32, 30–37 (2021). https://doi.org/10.1007/s00335-020-09856-y

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  • DOI: https://doi.org/10.1007/s00335-020-09856-y

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