Marion Horsch a , Peter H. Seeburg b , 1 , Thure Adler c , Juan Antonio Aguilar-Pimentel d , e , Lor

Marion Horsch a , Peter H. Seeburg b , 1 , Thure Adler c , Juan Antonio Aguilar-Pimentel d , e , Lore Becker f , Julia Calzada-Wack g , Lilian Garrett h , Alexander Götz i , Wolfgang Hans a , Miyoko Higuchi b , Sabine penang property talk M. Hölter h , Beatrix Naton a , Cornelia Prehn a , Oliver Puk h , Ildikó Rácz j , Birgit Rathkolb k , Jan Rozman l , Anja Schrewe a , m , Jerzy Adamski a , n , Dirk H. Busch c , Irene Esposito g , o , Jochen Graw h , Boris Ivandic m , Martin Klingenspor l , Thomas Klopstock penang property talk f , Martin penang property talk Mempel d , e , p , Markus Ollert d , Holger Schulz i , q , Eckhard Wolf k , Wolfgang Wurst h , r , s , t , Andreas Zimmer j , Valérie Gailus-Durner penang property talk a , Helmut Fuchs a , Martin Hrabě de Angelis a , n and Johannes Beckers penang property

talk a , n From the a Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, penang property talk Ingolstaedter Landstrasse penang property talk 1, 85764 Neuherberg, Germany, the b Departments of Molecular Neurobiology and Cell Physiology, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany, the c Institute for Medical Microbiology, Immunology, and Hygiene, Technical University Munich, Trogerstrasse 30, 81675 Munich, Germany, the d Clinical Research Division of Molecular and Clinical penang property talk Allergotoxicology, Department of Dermatology and Allergy and e Division of Environmental Dermatology and Allergy, TUM/Helmholtz Zentrum München GmbH, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany, the f Department of Neurology, Friedrich-Baur-Institut, Ludwig-Maximilians-University Munich, Ziemssenstrasse 1a, 80336 Munich, Germany, the g Institute of Pathology and h Institute of Developmental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Ingolstaedter Landstrasse penang property talk 1, 85764 Neuherberg, Germany, the i Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München GmbH, German penang property talk Research Center for Environmental penang property talk Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany, the j Institute penang property talk of Molecular Psychiatry, University of Bonn, Sigmund-Freud Strasse 25, 53125 Bonn, Germany, the k Chair for Molecular

Animal Breeding and Biotechnology, penang property talk Gene Center, Ludwig-Maximilians-University Munich, Feodor-Lynen-Strasse 25, 81377 Munich, penang property talk Germany, the l Molecular Nutritional Medicine, penang property talk Else Kröner-Fresenius Center, Technical University Munich, Gregor-Mendel-Strasse 2, 85350 Freising-Weihenstephan, Germany, the m Division

of Cardiology, Department

of Medicine III, University of Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany, the n Chair of Experimental Genetics, Technical University Munich, 85350 Freising-Weihenstephan, Germany, the o Institut für Allgemeine Pathologie und Pathologische Anatomie am Klinikum rechts der Isar, Technical University Munich, Trogerstraβe 18, 81675 Munich, Germany, p Department of Dermatology, Venerology, and Allergy, Georg-August-Universität Göttingen, Wilhelmsplatz 1, 37073 Goettingen, Germany, the q Chair of Developmental Genetics, Technical University Munich, 85350 Freising-Weihenstephan, Germany, the r Institute of Epidemiology I, Helmholtz Zentrum München GmbH, German Research Center for Environmental penang property talk Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany, the s Max-Planck Institut für Psychiatrie, Kraepelinstrasse 2-10, 80804 Munich, Germany, and the t Deutsches Zentrum für Neurodegenerative Erkrankungen e. V., Schillerstrasse 44, 80336 Munich, Germany 1 To whom correspondence should be addressed: Depts. of Molecular Neurobiology and Cell Physiology, Max-Planck Institute for Medical Research, penang property talk Jahnstrasse 29, 69120 Heidelberg, Germany. Tel.: 06221-486496 ; Fax: 06221-486110 ; E-mail: seeburg{at}mpimf-heidelberg.mpg.de .
ADAR2, an RNA editing enzyme that converts specific adenosines to inosines in certain penang property talk pre-mRNAs, often leading to amino acid substitutions in the encoded penang property talk proteins, penang property talk is mainly penang property talk 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 penang property talk when the critical edit is engineered penang property talk 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, penang property talk allergy parameters penang property talk and transcript profiles of brain. Gene knockout Gene regulation Mouse Mouse genetics RNA editing Phenotyping Systemic phenotyping
* This work was supported by the Bundesministerium für Bildung und Forschung (BMBF) Nationales Genomforsc