Comprehensive behavioral analyses of anoctamin1/TMEM16A-conditional knockout mice.

Abstract

AIMS: Anoctamin-1 (TMEM16A) is a calcium-activated chloride channel that is involved in numerous physiological conditions. Its role has been identified in electrophysiological and histological studies of genetic knockout animals. Recent cellular localization studies have shown that anoctamin-1 is co-expressed with presynaptic proteins, therefore its role in presynaptic terminals has been suggested. However, behavioral studies are lacking because conventional knockouts of anoctamin-1 are lethal after birth. In this study, we explored the role of anoctamin-1 in presynaptic terminals by analyzing the behavior of mice with conditional knockouts of anoctamin-1 in synapsin1-expressing cells. MAIN METHODS: Using a synapsin1-Cre system, we selectively ablated anoctamin-1 in synapsin1 expressing cells. The mice were used in the behavioral experiments when they were between 6 and 9 months of age. KEY FINDINGS: The mice with the conditional knockout of anoctamin-1 in synapsin1-expressing cells displayed impaired social behavior. In addition, the mice showed depressive-like behavior and decreased weight. However, these animals displayed normal locomotor activity, cognitive function, and motor coordination. SIGNIFICANCE: These results suggested that anoctamin-1 is involved in psychiatric behavior because of its role in the regulation of synaptic transmission in presynaptic terminals.