RNase H2 catalytic core Aicardi-Goutières syndrome-related mutant invokes cGAS-STING innate immune-sensing pathway in mice

The Journal of Experimental Medicine
Vladislav PokatayevRobert J Crouch

Abstract

The neuroinflammatory autoimmune disease Aicardi-Goutières syndrome (AGS) develops from mutations in genes encoding several nucleotide-processing proteins, including RNase H2. Defective RNase H2 may induce accumulation of self-nucleic acid species that trigger chronic type I interferon and inflammatory responses, leading to AGS pathology. We created a knock-in mouse model with an RNase H2 AGS mutation in a highly conserved residue of the catalytic subunit, Rnaseh2a(G37S/G37S) (G37S), to understand disease pathology. G37S homozygotes are perinatal lethal, in contrast to the early embryonic lethality previously reported for Rnaseh2b- or Rnaseh2c-null mice. Importantly, we found that the G37S mutation led to increased expression of interferon-stimulated genes dependent on the cGAS-STING signaling pathway. Ablation of STING in the G37S mice results in partial rescue of the perinatal lethality, with viable mice exhibiting white spotting on their ventral surface. We believe that the G37S knock-in mouse provides an excellent animal model for studying RNASEH2-associated autoimmune diseases.

References

Aug 30, 2008·Cell·Daniel B StetsonRuslan Medzhitov
Feb 21, 2009·The FEBS Journal·Susana M Cerritelli, Robert J Crouch
Mar 3, 2010·Proceedings of the National Academy of Sciences of the United States of America·Stephanie A Nick McElhinnyThomas A Kunkel
Dec 24, 2010·The Journal of Biological Chemistry·Martin A M ReijnsAndrew P Jackson
Apr 2, 2011·The Journal of Biological Chemistry·Stephanie R CoffinFred W Perrino
Jul 18, 2012·The Journal of Experimental Medicine·Bjoern HillerAxel Roers
Dec 15, 2012·Nature Reviews. Immunology·Michael S Diamond, Michael Farzan
Jan 29, 2013·Nucleic Acids Research·Hyongi ChonSusana M Cerritelli
Jul 23, 2013·The EMBO Journal·Jan RehwinkelCaetano Reis e Sousa
Apr 22, 2014·Nature Immunology·Hannah E Volkman, Daniel B Stetson
May 13, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea AblasserVeit Hornung
Aug 12, 2014·Biochemical Society Transactions·Martin A M Reijns, Andrew P Jackson
Nov 27, 2014·The EMBO Journal·Arun K MankanVeit Hornung
Dec 3, 2014·Cell Reports·Niamh M MannionMary A O'Connell
Dec 17, 2014·The Journal of Clinical Investigation·Claudia GüntherMin Ae Lee-Kirsch
Aug 1, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Elizabeth E GrayDaniel B Stetson
Aug 15, 2015·Science·Brian J LiddicoatCarl R Walkley
Sep 16, 2015·Proceedings of the National Academy of Sciences of the United States of America·Daxing GaoZhijian J Chen

❮ Previous
Next ❯

Citations

Apr 21, 2016·Immunity·Axel RoersVeit Hornung
May 8, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Andrea Ablasser, Muhammed F Gulen
Jun 30, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Maroof Hasan, Nan Yan
Sep 30, 2016·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Hanna KimRaphaela Goldbach-Mansky
Nov 1, 2016·Protein & Cell·Pengyan XiaZusen Fan
Mar 24, 2017·International Reviews of Immunology·Daisuke OriTaro Kawai
Feb 2, 2017·Annual Review of Immunology·John T CrowlDaniel B Stetson
Apr 13, 2017·Journal of Biochemistry·Misato BabaKiyoshi Yasukawa
Jan 10, 2018·Nucleic Acids Research·Jongsu ChoiKwangseog Ahn
Feb 16, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Zhao LeiTimothy R Billiar
Feb 20, 2018·Cellular & Molecular Immunology·Wei-Wei Luo, Hong-Bing Shu
Sep 2, 2017·The Journal of Cell Biology·Nelson O Gekara
Nov 28, 2018·Journal of Biochemistry·Motoki TsukiashiKiyoshi Yasukawa
Mar 1, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meng-Xin ZhangDandan Lin
Mar 25, 2016·The EMBO Journal·Matteo Gentili, Nicolas Manel
Dec 11, 2019·Nature Immunology·Andrea Ablasser, Sun Hur
Dec 20, 2019·Expert Review of Clinical Immunology·Davide TondutiSimona Orcesi
Nov 9, 2016·The Journal of Experimental Medicine·Mathieu P Rodero, Yanick J Crow
Aug 24, 2018·The Journal of Experimental Medicine·Kun YangNan Yan
Apr 7, 2018·The Journal of Experimental Medicine·Tuo Li, Zhijian J Chen
Jun 10, 2017·Journal of Inflammation·Yang LiEndre Kiss-Toth
Jul 17, 2018·Briefings in Functional Genomics·Kenji KojimaKiyoshi Yasukawa
May 31, 2018·International Journal of Molecular Sciences·Chin-An YangJan-Gowth Chang
Sep 29, 2019·Nature Reviews. Immunology·Tao GongRongbin Zhou
Jun 17, 2020·Cell Research·Seoyun YumZhijian J Chen
Nov 5, 2016·Annual Review of Medicine·Min Ae Lee-Kirsch
May 6, 2017·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Hiroki KatoTakashi Fujita
May 30, 2019·Frontiers in Immunology·Tomas MustelinNatalia V Giltiay
Sep 19, 2019·Journal of Biochemistry·Takuto NishimuraKiyoshi Yasukawa
Jul 8, 2020·Genes·Clara Forrer Charlier, Rodrigo A P Martins
Aug 9, 2020·Nature Reviews. Genetics·Dali ZongAndré Nussenzweig
Aug 25, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Martin AchleitnerRayk Behrendt
May 6, 2017·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Nan Yan
Mar 9, 2019·Science·Andrea Ablasser, Zhijian J Chen
May 9, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Jung-Hyun LeeMichaela U Gack

❮ Previous
Next ❯

Methods Mentioned

BETA
RNA-seq
FACS
PCR
FCS

Software Mentioned

DAVID

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Daxing GaoZhijian J Chen
European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society
Pierre LebonFlore Rozenberg
Anales de pediatría : publicación oficial de la Asociación Española de Pediatría (A.E.P.)
A de la Fuente JuárezR Porta Ribera
© 2022 Meta ULC. All rights reserved