Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice
Autor: | Oliver Puk, Thomas Klopstock, Peter H. Seeburg, Thure Adler, Martin Klingenspor, Jan Rozman, Juan Antonio Aguilar-Pimentel, Anja Schrewe, Sabine M. Hölter, Holger Schulz, Martin Mempel, Andreas Zimmer, Irene Esposito, Martin Hrabě de Angelis, Miyoko Higuchi, Lore Becker, Jochen Graw, Beatrix Naton, Wolfgang Hans, Johannes Beckers, Helmut Fuchs, Marion Horsch, Markus Ollert, Lillian Garrett, Wolftgang Wurst, Alexander Götz, Cornelia Prehn, Eckhard Wolf, Dirk H. Busch, Boris Ivandic, Julia Calzada-Wack, Ildiko Racz, Jerzy Adamski, Birgit Rathkolb, Valerie Gailus-Durner |
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Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Adenosine Deaminase
physiology [RNA Editing] AMPA receptor Biochemistry no keywords 03 medical and health sciences metabolism [Adenosine Deaminase] Mice 0302 clinical medicine RNA Precursors Animals GRIA2 Receptors AMPA Allele Molecular Biology Gene Gene knockout 030304 developmental biology Regulation of gene expression Genetics Mice Knockout 0303 health sciences metabolism [RNA Precursors] biology metabolism [Receptors AMPA] physiology [Organ Specificity] ADARB1 protein human RNA-Binding Proteins Cell Biology Phenotype genetics [Adenosine Deaminase] RNA editing Organ Specificity ddc:540 biology.protein RNA genetics [RNA Precursors] glutamate receptor ionotropic AMPA 2 RNA Editing genetics [Receptors AMPA] 030217 neurology & neurosurgery |
Zdroj: | The journal of biological chemistry 286(21), 18614-18622 (2011). doi:10.1074/jbc.M110.200881 The Journal of Biological Chemistry J. Biol. Chem. 286, 18614-18622 (2011) |
DOI: | 10.1074/jbc.M110.200881 |
Popis: | 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(-/-)/Gria2(R/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(-/-)/Gria2(R/R) mouse line, and Gria2(R/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. |
Databáze: | OpenAIRE |
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