Hyperphagia-mediated Obesity in Transgenic Mice Misexpressing the RNA-editing Enzyme ADAR2*

ADAR2 is a double-stranded RNA-specific adenosine deaminase involved in the editing of mammalian RNAs by the site-specific conversion of adenosine to inosine. To examine the physiologic consequences resulting from ADAR2 misexpression, we have generated mutant mice expressing either wild-type or deaminase-deficient ADAR2 transgenes under the control of the human cytomegalovirus promoter. Transgenic mice expressing either wild-type or inactive ADAR2 isoforms demonstrated adult onset obesity characterized by hyperglycemia, hyperleptinemia, and increased adiposity. Paired feeding analysis revealed that mutant mice on caloric restriction had a growth rate and body composition indistinguishable from wild-type littermates, indicating that the observed obesity predominantly results from hyperphagia rather than a metabolic derangement. The observation that expression of catalytically inactive ADAR2 also is capable of producing an obese phenotype in mutant animals suggests that ADAR2 may possess additional biological activities beyond those required for the site-selective deamination of adenosine or may interfere with the actions of other double-stranded RNA-specific binding proteins in the cell.

• Publication year

  2007

• Venue

  Journal of Biological Chemistry

• Publication date

  2007-08-03

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M700265200PMID 17567573
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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