The mTRPC2 channel is essential for function of the mouse vomeronosal organ (VNO) and blockade of this channel in murine sperm results in a reduction in Ca²⁺ influx and concomitant reduction in the rate of acrosome reaction. But due to the diverse array of mRNA species derived form the mTrpc2 locus there is controversy surrounding the sites of mRNA expression the nature of the open reading frame of these transcript and hence sites of channel translation and function. In order to address these questions we have undertaken a detailed analysis of the murine trpc2 locus.

We initially identified two further 5′ coding exons in the murine trpc2 locus that have allowed us to extend the coding region of the trpc2 transcripts derived from the distal promoter in the locus. In addition to extending the open reading frame of the channel encoding mRNA species derived from this promoter these additional exons introduce an upstream open reading frame that would be available for translation in Trpc2 transcripts that are expressed in multiple tissues. Unlike the mRNAs that encode channel proteins these mRNA species include intronic sequence that would introduce stop codons so preventing the translation of a channel protein from these transcripts. A novel feature of this new reading frame is that it is conserved and expressed in the human, while the Trpc2 channel transcripts are not. So while the human lacks Trpc2 transcripts that can encode a channel, this non-channel transcript encodes a protein that is highly conserved between mouse and human. A comparison of the human-mouse synteny maps indicates that a break occurs within the trpc2 locus and it may be this event, rather than neutral selection, that underlies the loss of the trpc2 channel transcripts in the higher primates.