Development of a Mouse Reporter Strain for the Purinergic P2X₂ Receptor

The ATP-sensitive P2X₂ ionotropic receptor plays a critical role in a number of signal processes including taste and hearing, carotid body detection of hypoxia, the exercise pressor reflex and sensory transduction of mechanical stimuli in the airways and bladder. Elucidation of the role of P2X₂ has been hindered by the lack of selective tools. In particular, detection of P2X₂ using established pharmacological and biochemical techniques yields dramatically different expression patterns, particularly in the peripheral and central nervous systems. Here, we have developed a knock-in P2X₂-cre mouse, which we crossed with a cre-sensitive tdTomato reporter mouse to determine P2X₂ expression. P2X₂ was found in more than 80% of nodose vagal afferent neurons, but not in jugular vagal afferent neurons. Reporter expression correlated in vagal neurons with sensitivity to α,β methylene ATP (αβmATP). P2X₂ was expressed in 75% of petrosal afferents, but only 12% and 4% of dorsal root ganglia (DRG) and trigeminal afferents, respectively. P2X₂ expression was limited to very few cell types systemically. Together with the central terminals of P2X₂-expressing afferents, reporter expression in the CNS was mainly found in brainstem neurons projecting mossy fibers to the cerebellum, with little expression in the hippocampus or cortex. The structure of peripheral terminals of P2X₂-expressing afferents was demonstrated in the tongue (taste buds), carotid body, trachea and esophagus. P2X₂ was observed in hair cells and support cells in the cochlear, but not in spiral afferent neurons. This mouse strain provides a novel approach to the identification and manipulation of P2X₂-expressing cell types.