Reduced vomeronasal receptor diversity and impaired pheromone detection in Tex15 knockout mice

Abstract

The mouse vomeronasal organ (VNO) detects pheromones, which provide vital information needed to find a mate, detect predators, or alert to the presence of an intruder. Within the VNO, pheromones are sensed by two families of G-protein Coupled Receptors (GPCRs) the type 1 and type 2 vomeronasal receptors (V1Rs and V2Rs). However, little is known about the regulatory mechanisms that control the expression of V1R and V2R genes by vomeronasal sensory neurons (VSNs). Here we identify a transcriptional repressor, Testis-expressed gene 15 (Tex15), that regulates vomeronasal receptor gene choice and is required for the proper functioning of the vomeronasal system in regulating male behavior. We find that Tex15 is transiently expressed by VSN precursors prior to strong VR gene expression. The absence of Tex15 results in a pervasive change in the expression of V1R and V2R genes, which results in a less diverse repertoire of VR expressing cells and includes a dramatic reduction in the expression of specific receptors that have been tied to intermale aggression. Accordingly, Tex15 knockout mice exhibit lowered activation in the Accessory Olfactory Bulb (AOB) after exposure to male odorants, and a loss of stereotyped aggression between male mice. Taken together, these results show that Tex15 plays a critical role in pheromone sensing by ensuring that VSNs express a diverse set of receptor proteins.