Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice

ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading to amino acid substitutions in the encoded proteins, is mainly expressed in brain. Of all ADAR2-mediated edits, a single one in the pre-mRNA of the AMPA receptor subunit GluA2 is essential...

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Hauptverfasser: Horsch, Marion (VerfasserIn) , Seeburg, Peter H. (VerfasserIn) , Adler, Thure (VerfasserIn) , Aguilar-Pimentel, Juan Antonio (VerfasserIn) , Becker, Lore (VerfasserIn) , Calzada-Wack, Julia (VerfasserIn) , Garrett, Lilian (VerfasserIn) , Götz, Alexander (VerfasserIn) , Hans, Wolfgang (VerfasserIn) , Higuchi, Miyoko (VerfasserIn) , Hölter, Sabine M. (VerfasserIn) , Naton, Beatrix (VerfasserIn) , Prehn, Cornelia (VerfasserIn) , Puk, Oliver (VerfasserIn) , Rácz, Ildikó (VerfasserIn) , Rathkolb, Birgit (VerfasserIn) , Rozman, Jan (VerfasserIn) , Schrewe, Anja (VerfasserIn) , Adamski, Jerzy (VerfasserIn) , Busch, Dirk H. (VerfasserIn) , Esposito, Irene (VerfasserIn) , Graw, Jochen (VerfasserIn) , Ivandic, Boris (VerfasserIn) , Klingenspor, Martin (VerfasserIn) , Klopstock, Thomas (VerfasserIn) , Mempel, Martin (VerfasserIn) , Ollert, Markus (VerfasserIn) , Schulz, Holger (VerfasserIn) , Wolf, Eckhard (VerfasserIn) , Wurst, Wolfgang (VerfasserIn) , Zimmer, Andreas (VerfasserIn) , Gailus-Durner, Valérie (VerfasserIn) , Fuchs, Helmut (VerfasserIn) , de Angelis, Martin Hrabě (VerfasserIn) , Beckers, Johannes (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 5 April 2011
In: The journal of biological chemistry
Year: 2011, Jahrgang: 286, Heft: 21, Pages: 18614-18622
ISSN:1083-351X
DOI:10.1074/jbc.M110.200881
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1074/jbc.M110.200881
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0021925820511186
Volltext
Verfasserangaben:Marion Horsch, Peter H. Seeburg, Thure Adler, Juan Antonio Aguilar-Pimentel, Lore Becker, Julia Calzada-Wack, Lilian Garrett, Alexander Götz, Wolfgang Hans, Miyoko Higuchi, Sabine M. Hölter, Beatrix Naton, Cornelia Prehn, Oliver Puk, Ildikó Rácz, Birgit Rathkolb, Jan Rozman, Anja Schrewe, Jerzy Adamski, Dirk H. Busch, Irene Esposito, Jochen Graw, Boris Ivandic, Martin Klingenspor, Thomas Klopstock, Martin Mempel, Markus Ollert, Holger Schulz, Eckhard Wolf, Wolfgang Wurst, Andreas Zimmer, Valérie Gailus-Durner, Helmut Fuchs, Martin Hrabě de Angelis, and Johannes Beckers

MARC

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520 |a ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain pre-mRNAs, often leading to amino acid substitutions in the encoded proteins, is mainly expressed in brain. Of all ADAR2-mediated edits, a single one in the pre-mRNA of the AMPA receptor subunit GluA2 is essential for survival. Hence, early postnatal death of mice lacking ADAR2 is averted when the critical edit is engineered into both GluA2 encoding Gria2 alleles. Adar2−/−/Gria2R/R mice display normal appearance and life span, but the general phenotypic effects of global lack of ADAR2 have remained unexplored. Here we have employed the Adar2−/−/Gria2R/R mouse line, and Gria2R/R mice as controls, to study the phenotypic consequences of loss of all ADAR2-mediated edits except the critical one in GluA2. Our extended phenotypic analysis covering ∼320 parameters identified significant changes related to absence of ADAR2 in behavior, hearing ability, allergy parameters and transcript profiles of brain. 
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