Since itch can be a subjective sensation, markedly affected by psychological conditions or sometimes originate in the central nervous system, the mechanisms of neuronal processing of itch signaling in the central nervous system should be studied. Therefore, we examined itch-related behaviors and nervous gene expressions of NC mice, which show severe dermatitis and atopy-like changes in inflammatory cells. Some NC mice spontaneously scratched their bodies and showed skin lesions, such as eczema, bleeding and alopecia from 2-6 months after birth. The mice with skin lesions scratched mainly the face, ears and rostral part of the body throughout the day, using their hind paws . The average scratching frequency was 126.7 +/- 36.8 (n = 4) and 5.3 +/- 4.7 (n = 3) per h in skin-lesioned and non-lesioned control mice, respectively. A differential display analysis of gene expressions in several regions in central and peripheral nervous systems was performed between these scratching and control groups. One of the genes that was expressed at a higher level in a scratching group than in the control group was myocyte-specific enhancer binding factor (MEF) 2C, in the cerebral cortex. The scratching was inhibited by intracerebroventricular injection of antisense oligodeoxynucleotide for MEF2C. These results raise the possibility that MEF2C may be involved in the sensation or perception of itch in the cerebral cortex.