A novel Nav1.8-FLPo driver mouse for intersectional genetics to uncover the functional significance of primary sensory neuron diversity

一种新型 Nav1.8-FLPo 驱动小鼠,用于交叉遗传学揭示初级感觉神经元多样性的功能意义

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作者:Pascale Malapert, Guillaume Robert, Elena Brunet, Jean Chemin, Emmanuel Bourinet, Aziz Moqrich

Abstract

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 Nav1.8Ires-FLPo mice with the AdvillinCre and RC::FL-hM3Dq mouse lines in an intersectional genetics approach, we were able to obtain somatodendritic expression of hM3Dq-mCherry selectively in the Nav1.8 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 Nav1.8Ires-FLPo mouse model will be a valuable tool for extending our understanding of the in vivo functional specialization of neuronal subsets of the Nav1.8 lineage for which inducible Cre lines are available.

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