title: Requirement of the RNA-editing enzyme ADAR2 for normal physiology in mice.
abstract: 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.
authors.affiliation: Institute of Experimental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Horsch
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: Thure
authors.initials: T
authors.lastname: Adler
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Aguilar-Pimentel
authors.forename: Lore
authors.initials: L
authors.lastname: Becker
authors.forename: Julia
authors.initials: J
authors.lastname: Calzada-Wack
authors.forename: Lilian
authors.initials: L
authors.lastname: Garrett
authors.forename: Alexander
authors.initials: A
authors.lastname: Götz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hans
authors.forename: Miyoko
authors.initials: M
authors.lastname: Higuchi
authors.forename: Sabine M
authors.initials: SM
authors.lastname: Hölter
authors.forename: Beatrix
authors.initials: B
authors.lastname: Naton
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Oliver
authors.initials: O
authors.lastname: Puk
authors.forename: Ildikó
authors.initials: I
authors.lastname: Rácz
authors.forename: Birgit
authors.initials: B
authors.lastname: Rathkolb
authors.forename: Jan
authors.initials: J
authors.lastname: Rozman
authors.forename: Anja
authors.initials: A
authors.lastname: Schrewe
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.forename: Boris
authors.initials: B
authors.lastname: Ivandic
authors.forename: Martin
authors.initials: M
authors.lastname: Klingenspor
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Martin
authors.initials: M
authors.lastname: Mempel
authors.forename: Markus
authors.initials: M
authors.lastname: Ollert
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Wolf
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Helmut
authors.initials: H
authors.lastname: Fuchs
authors.forename: Martin Hrabe
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Johannes
authors.initials: J
authors.lastname: Beckers
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity / Q000502:physiology; D017393:RNA Editing / Q000502:physiology*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism
chemical_list: D012322:RNA Precursors; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; C104722:glutamate receptor ionotropic, AMPA 2