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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.

SUBMITTER: Horsch M 

PROVIDER: S-EPMC3099677 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Horsch Marion M   Seeburg Peter H PH   Adler Thure T   Aguilar-Pimentel Juan Antonio JA   Becker Lore L   Calzada-Wack Julia J   Garrett Lilian L   Götz Alexander A   Hans Wolfgang W   Higuchi Miyoko M   Hölter Sabine M SM   Naton Beatrix B   Prehn Cornelia C   Puk Oliver O   Rácz Ildikó I   Rathkolb Birgit B   Rozman Jan J   Schrewe Anja A   Adamski Jerzy J   Busch Dirk H DH   Esposito Irene I   Graw Jochen J   Ivandic Boris B   Klingenspor Martin M   Klopstock Thomas T   Mempel Martin M   Ollert Markus M   Schulz Holger H   Wolf Eckhard E   Wurst Wolfgang W   Zimmer Andreas A   Gailus-Durner Valérie V   Fuchs Helmut H   de Angelis Martin Hrabe MH   Beckers Johannes J  

The Journal of biological chemistry 20110405 21


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 appea  ...[more]

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