Although Tlx3cko mice showed significant decreases in the expression of several molecules related to chronic itch, including Hrh1, IL31ra and MrgprA3, obvious spontaneous scratching was still observed in Tlx3cko mice with dry skin or ACD, suggesting that the chronic itch was evoked by complicated factors and that the mutants retained alternative pathways for relaying chronic itch signals. The gene discussed is HRH1; the disease is granular corneal dystrophy type II.