Mouse models to elucidate the functional roles of adenosine-to-inosine editing

Abstract

The conversion of adenosine to inosine (A-to-I) by RNA editing is a widespread RNA processing event by which genomically encoded sequences are altered through site-specific deamination of adenosine residue(s) in RNA transcripts through the actions of a family of double-stranded RNA-specific adenosine deaminases (ADARs). While significant advances have been made regarding the functional consequences of A-to-I editing using heterologous expression systems, the physiological relevance of such RNA modifications in mammals has been addressed effectively using gene-targeting strategies in mice via homologous recombination in embryonic stem (ES) cells. These gene-targeting approaches have allowed the generation of mutant mouse strains in which site-specific editing events can be fixed in the fully edited or nonedited state for individual ADAR targets, expression of ADAR proteins can be selectively ablated, or a combination of ADAR elimination and ADAR target modification can be used for a more in-depth understanding of the biological consequences of A-to-I editing dysregulation.