Hypomorphic Mutation in the Hairless Gene Accelerates Pruritic Atopic Skin Caused by Feeding a Special Diet to Mice

The study investigated the role of a hypomorphic mutation in the hairless (Hr) gene in the development of diet-induced pruritic atopic dermatitis (AD) in mice. Five different mouse strains were fed a special diet (HR-AD) for 12 weeks, and it was found that HR-1 mice, which carry the Hr mutation, developed more severe and earlier onset of AD symptoms compared to other strains. A newly generated hairless congenic strain (ICR-Hrhr) confirmed that the Hr mutation was essential for the full development of diet-induced pruritic atopic skin. The Hr gene product was shown to interact with the vitamin D receptor (VDR), suggesting a mechanistic link in AD development. The study concluded that the Hr mutation, combined with dietary deficiencies of polyunsaturated fatty acids (PUFAs) and starch, accelerates AD progression, highlighting the genetic predisposition to AD in Hr mutant mice and suggesting potential therapeutic targets.