A novel Na _v1.8-FLPo driver mouse for intersectional genetics to uncover the functional significance of primary sensory neuron diversity

Summary

The recent development of single-cell and single-nucleus RNA sequencing has highlighted the extraordinary diversity of dorsal root ganglia neurons. However, the few available genetic tools limit our understanding of the functional significance of this heterogeneity. We generated a new mouse line expressing the flippase recombinase from the scn10a locus. By crossing Na _v1.8 ^Ires−FLPo mice with the Advillin ^Cre and RC::FL-hM3Dq mouse lines in an intersectional genetics approach, we were able to obtain somatodendritic expression of hM3Dq-mCherry selectively in the Na _v1.8 lineage. The bath application of clozapine N-oxide triggered strong calcium responses selectively in mCherry ⁺ neurons. The intraplantar injection of CNO caused robust flinching, shaking, and biting responses accompanied by strong cFos activation in the ipsilateral lumbar spinal cord. The Na _v1.8 ^Ires−FLPo mouse model will be a valuable tool for extending our understanding of the in vivo functional specialization of neuronal subsets of the Na _v1.8 lineage for which inducible Cre lines are available.

Graphical abstract

Highlights

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  Generation of a new mouse line expressing the flippase recombinase in Na _v1.8 lineage

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  CNO triggers strong calcium response in Na _v1.8 ^Ires−FLPo::Advillin ^Cre:: RC::FL-hM3Dq mice

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  Intraplantar injection of CNO causes robust nocifensive responses and strong spinal cFos

Abstract

Neuroscience, Molecular biology, Cellular biology