The sense of light touch is critical for hand dexterity that allows mammals to recognize and grasp objects. Psychophysical and neurophysiological studies have shown that different qualities of touch are encoded by somatosensory neurons with distinctive coding properties (Johnson, 2001). Particularly important for tactile discrimination, shapes and textures are encoded by Merkel cell-neurite complexes, which mediate slowly adapting type I (SAI) responses (Iggo and Muir, 1969; Woodbury and Koerber, 2007). Merkel cells, which are found in fingertips and other highly touch-sensitive skin areas (Halata et al., 2003), are enigmatic skin cells first described in 1875 (Merkel, 1875). The role that these cells play in SAI responses has been the subject of controversy for 40 years (Halata et al., 2003). Based on morphology, Merkel cells are proposed to be mechanosensory cells (Halata et al., 2003; Haeberle and Lumpkin, 2008). If this model is correct, Merkel cells should 1) transduce force into membrane-potential changes that gate voltage-activated ion channels and 2) signal afferent neurons through synaptic transmission. Functional studies testing these predictions in intact skin have produced conflicting results (Halata et al., 2003; Haeberle and Lumpkin, 2008). To tackle these questions, my laboratory uses a combination of mouse genetics, simplified in vitro systems and intact electrophysiological recordings. In vitro studies have demonstrated that Merkel cells are intrinsically force-sensitive and that voltage-activated channels open downstream of mechanical stimuli. Using genomics, we identified hundreds of highly enriched Merkel-cell transcripts. Importantly, many encode neuronal transcription factors, ion channels and synaptic proteins. Collectively, these results suggest that Merkel cells are capable of serving as touch receptor cells and pave the way to discover transduction mechanisms. To determine whether Merkel cells are necessary for touch responses in the intact skin, we used Cre-loxP technology to generate mice that selectively and completely lack Merkel cells in the body skin and footpads. We then used an ex vivo skin-nerve preparation to survey the classes of touch-sensitive afferents in the saphenous nerve. Although we found no significant differences in mechanosensitive C- and A-delta afferent fibers, we observed a complete loss of SAI responses among A-beta afferents in mice lacking Merkel cells (0/26 afferents) compared with wild-type mice (8/39 afferents; P<0.02, Fisher’s exact test). These results demonstrate that Merkel cells are required for appropriate sensory coding in SAI afferents.