A 3.7 kb fragment of the mouse Scn10a gene promoter directs neural crest but not placodal lineage EGFP expression in a transgenic animal.

Under physiological conditions, the voltage-gated sodium channel Na v 1.8 is expressed almost exclusively in primary sensory neurons. The mechanism restricting Na v 1.8 expression is not entirely clear, but we have previously described a 3.7 kb fragment of the Scn10a promoter capable of recapitulating the tissue-specific expression of Na v 1.8 in transfected neurons and cell lines (Puhl and Ikeda, 2008). To validate these studies in vivo , a transgenic mouse encoding EGFP under the control of this putative sensory neuron specific promoter was generated and characterized in this study. Approximately 45% of dorsal root ganglion neurons of transgenic mice were EGFP-positive (mean diameter = 26.5 μm). The majority of EGFP-positive neurons bound isolectin B4, although a small percentage (∼10%) colabeled with markers of A-fiber neurons. EGFP expression correlated well with the presence of Na v 1.8 transcript (95%), Na v 1.8-immunoreactivity (70%), and TTX-R I Na (100%), although not all Na v 1.8-expressing neurons expressed EGFP. Several cranial sensory ganglia originating from neurogenic placodes, such as the nodose ganglion, failed to express EGFP, suggesting that additional regulatory elements dictate Scn10a expression in placodal-derived sensory neurons. EGFP was also detected in discrete brain regions of transgenic mice. Quantitative PCR and Na v 1.8-immunoreactivity confirmed Na v 1.8 expression in the amygdala, brainstem, globus pallidus, lateral and paraventricular hypothalamus, and olfactory tubercle. TTX-R I Na recorded from EGFP-positive hypothalamic neurons demonstrate the usefulness of this transgenic line to study novel roles of Na v 1.8 beyond sensory neurons. Overall, Scn10a -EGFP transgenic mice recapitulate the majority of the Na v 1.8 expression pattern in neural crest-derived sensory neurons.