Ano10-flox Mouse

Ano10, also known as TMEM16K, is a transmembrane protein and member of the anoctamin family. It exhibits functional duality with ion channel and phospholipid scrambling activities. Ano10 is involved in processes like endosomal sorting, spindle assembly, and calcium signalling [2]. Calcium is necessary for its protein activation in either activity. Dysregulation of calcium signalling in Purkinje cells due to Ano10 defects is proposed as the main mechanism leading to spinocerebellar ataxia autosomal recessive type 10 (SCAR10) [2].

Ano10 knockout in epithelial cells leads to defective ion transport, attenuated volume regulation and deranged Ca2+ signalling. Intestinal epithelial cells from Ano10 null mice are reduced in size and show almost abolished spontaneous and TNFα -induced apoptosis. Similar defects are found in mouse peritoneal Ano10 null macrophages and in human THP1 macrophages with reduced Ano10 expression [3]. Biallelic pathogenic variants in the Ano10 gene cause autosomal recessive progressive ataxia (ATX-Ano10), with most patients having loss-of-function variants [1].

In conclusion, Ano10 plays essential roles in ion transport, calcium signalling, and cell-related processes like apoptosis. Ano10 knockout models have been crucial in revealing its role in causing autosomal recessive progressive ataxia and associated cellular defects, thus deepening our understanding of related disease mechanisms [1,3].