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bioRxiv · 10.1101/2025.03.18.643951

Genetic targeting of myelinated primary afferent neurons using a new NefhCreERT2 knock-in mouse

Chen, J. C.·Kaczmarczyk, L.·de Faria, F. M.·Szczot, M.·Jackson, W. S.·Larsson, M.
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Abstract

Primary afferent neurons that convey somatosensory modalities comprise two large, heterogeneous populations: small-diameter neurons that give rise to slowly conducting unmyelinated axonal C fibers and medium-to-large diameter neurons with fast myelinated A fibers. Despite these two major groupings, tools to differentiate between unmyelinated and myelinated primary afferent fibers by genetic targeting have not been available; in particular, whereas numerous mouse driver lines exist to target different C fiber populations, genetic tools that target myelinated primary afferent populations are scarce. Here we describe a knock-in mouse line expressing tamoxifen-dependent CreERT2 under control of the Nefh gene, which encodes neurofilament heavy chain (NFH or NF200), a protein that is highly enriched in myelinated fibers. This mouse enables highly selective and efficient recombination of Cre-dependent reporters for functional and anatomical interrogation of myelinated fibers while excluding unmyelinated C fibers. In combination with other recombinase-expressing mouse lines, this genetic tool will be valuable for intersectional targeting of subpopulations of myelinated primary afferent fibers.

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Chen, J. C., Kaczmarczyk, L., de Faria, F. M., Szczot, M., Jackson, W. S., Larsson, M.. 2025-03-18. Genetic targeting of myelinated primary afferent neurons using a new NefhCreERT2 knock-in mouse. https://doi.org/10.1101/2025.03.18.643951

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