TMEM16A (Anoctamin 1) was identified as Ca2+-activated Cl- channel by three groups in 2008. It belongs to a gene family with ten members, but it is currently unclear whether all of them display Cl- channel function (some of them work as lipid scramblases). In our studies we have focused on TMEM16B (Ano2), which in contrast to TMEM16A (Ano1) shows a very restricted expression with high expression levels in the nose and in the retina. By generating and analyzing Ano2 knock-out mice we demonstrated  that Ano2 is the long-sought Ca2+-activated Cl- channel of olfactory sensory neurons which was thought to amplify olfactory responses by a factor of ten. Surprisingly, however, the transepithelial electrical response of the main olfactory epithelium to odorants was almost normal, and no effect of the loss of Ano2 on olfaction could be found in behavioral olfactometry experiments. We thus conclude that Ca2+-activated Cl- channels are dispensable for olfaction .
Whereas Ano2 is the only Ca2+-activated Cl- channel in sensory neurons of the main olfactory epithelium, the vomeronasal organ (VNO) of the mouse, which is specialized in detecting socially important moieties such as pheromones, expresses both Ano1 and Ano2. Using double KOs, we clarified the relative contribution of these channels to VNO physiology.