To address this question, we use the mouse as model organism. The mouse has several advantages such as generation of transgenic models in which a gene can be inactivated, ectopically overexpressed or a combination of both in a tissue specific manner. The mouse genome is very close to that of humans and many debilitating human pathological conditions can be mimicked in mice.

FOR SPECIALISTS

High magnification of a hair follicle surrounded by an EGFP-expressing C-LTMR fiber

We have designed a strategy aimed at expanding the molecular characterization of the nociceptive system by identifying new factors expressed in specific subsets of dorsal root ganglion neurons. For each of these newly identified neuronal markers, a sophisticated mouse model is being engineered. In these mice, each candidate gene is being conditionally inactivated by knocking-in an inducible killer molecule that will specifically ablate discrete subpopulations of nociceptive neurons marked by each of our candidate genes.

EGFP-expressing C-LTMRs peripheral fiber nicely connecting mouse hair follicles in the hairy skin

These mice models, in addition to deciphering the function of our candidate genes in the specification and function of primary sensory neurons, they will be used as unique cell ablation models, providing new insights into the functional specialization of discrete subclasses of primary nociceptive neurons. Conditional inactivation of a given target gene, and the use of the regulatory elements of this same target gene to drive the expression of an inducible killer molecule in a living animal represents the most innovative, specific and powerful approach to determine functions of specific neuronal subtypes.

Results emanating from this work will provide hints on how a precise neuronal subtype is generated, how it matures and what kind of particular sensory modalities it perceives.