Conditional deletion of Tmem63b does not impact mouse voiding behavior

Abstract

The proper function of the lower urinary tract depends on its ability to sense and react to mechanical forces as urine is produced, transported, stored, and eliminated; however, our current understanding of the mechanosensors involved in these events is limited. TMEM63 ion channels are reported to function as mechanosensors/osmosensors in other organs, and our studies revealed that the primary site of Tmem63a and Tmem63b gene expression and TMEM63B protein expression in the mouse bladder wall was the urothelium. Despite this localization, voiding behavior in conditional urothelial Tmem63b knockout mice, assessed using a video-monitored void-spot screening assay, was not significantly different from control mice, even when the urothelium was stressed by exposure to cyclophosphamide. We further observed that dorsal root ganglia sensory neurons, including those innervating the bladder, were also sites of Tmem63a , Tmem63b , and TMEM63B expression. Again, voiding behavior was not impacted in conditional sensory neuron Tmem63b knockout mice, treated or not with cyclophosphamide. Our studies reveal that the urothelium and dorsal root ganglia are sites of Tmem63a , Tmem63b , and TMEM63B expression, but deletion of Tmem63b alone in these tissues does not result in a demonstrable voiding phenotype.