Genetic exploration of the role of acid-sensing ion channels

• Published in: Neuropharmacology Vol. 94; pp. 99 - 118
• Main Authors: Lin, Shing-Hong, Sun, Wei-Hsin, Chen, Chih-Cheng
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2015
• Subjects: Acid Sensing Ion Channels - genetics; Acid Sensing Ion Channels - metabolism; Animals; ASIC; Gene Knockout Techniques; Gene targeting; Knockout; Mechanotransduction; Mice, Knockout; Pain; Phenotype; ASIC; Phenotype; Mechanotransduction; Gene targeting; Pain; Knockout
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2014.12.011

Advanced gene targeting technology and related tools in mice have been incorporated into studies of acid-sensing ion channels (ASICs). A single ASIC subtype can be knocked out specifically and screened thoroughly for expression in the nervous system at the cellular level. Mapping studies have further shed light on the initiation and identification of related behavioral phenotypes. Here we review studies involving genetically engineered mouse models used to investigate the physiological function of individual ASIC subtypes: ASIC1 (and ASIC1a), ASIC2, ASIC3 and ASIC4. We discuss the detailed expression studies and significant phenotypes revealed with gene knockout for most known Asic subtypes. Each strategy designed to manipulate mouse genetics has advantages and disadvantages. We discuss the limitations of these Asic-knockout models and propose future directions to solve the genetic issues. This article is part of the Special Issue entitled ‘Acid-Sensing Ion Channels in the Nervous System’. •A comprehensive list of genetically engineered mouse models of ASICs is reviewed.•We summarize the ASIC expression studies validated with ASIC-subtype mutant mice.•We summarize important phenotypes found in mice lacking ASIC1a, ASIC2, or ASIC3.•We propose strategies how to probe phenotypes in conditional knockouts of ASICs.