TMEM206 gene knockout improves balance performance in SCA1 transgenic mice.

TMEM206 was identified as a conserved chloride channel that underlies widely expressed, proton-activated, outwardly rectifying chloride currents. Spinocerebellar ataxia type 1 (SCA1) is one of polyglutamine diseases, and is characterized as a progressive and autosomal dominant genetic disease, which is caused by an increasing number of CAG repeats in the ataxin-1 gene. TMEM206 was confirmed to interact with ataxin-1. This study suggests that TMEM206-ataxin-1 interaction might involve in the pathological mechanisms of SCA1. To elucidate the mechanisms of SCA1 involved in proton-activated chloride channel gating, we bred TMEM206 knockout mice using SCA1 model mice. Motor coordination and balance in mice was evaluated using rotarod test and grip strength. These studies showed that genetic depletion of TMEM206 has slight impacts on the SCA1 mice weight, and partially improves motor incoordination in Atxn1154Q/2Q mice. No alteration in grip strength was found in Atxn1154Q/2Q mice with depletion of the TMEM206 gene. Our studies indicate that the TMEM206 knockout appears to emerge as a potential therapy method for SCA1 mice.