The alopecia areata phenotype is induced by the water avoidance stress test in cchcr1-deficient mice

ABSTRACTBackgroundWe recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene within the alopecia areata (AA) risk haplotype; mice engineered to carry the risk allele displayed a hair loss phenotype.ObjectiveTo further investigate the involvement of the CCHCR1 gene in AA pathogenesis.MethodsWe developed an AA model using C57BL/6N cchcr1 gene knockout mice. Mice (6-8 weeks) were divided into two groups: cchcr1-/- mice and wild-type (WT) mice. Both groups were subjected to a water avoidance stress (WAS) test.ResultsEight weeks after the WAS test, 25% of cchcr1 mice exhibited noninflammatory foci of alopecia on the dorsal skin. The foci resembled human AA in terms of gross morphology, trichoscopic findings and histological findings.ConclusionsOur results strongly suggest that CCHCR1 is associated with AA pathogenesis and that cchcr1-/- mice are a good model for investigating AA.Author summaryAlopecia areata is thought to affect 1-2% of the population. In severe alopecia areata, changes in appearance significantly reduce the patient’s quality of life, but there is no established treatment. Its pathogenic mechanism is thought to cause an autoimmune disease of the hair bulb of growing hair. Many genes and factors associated with AA onset form a background that easily causes such an immune reaction, and the causative genes related to alopecia areata are being elucidated worldwide. We were able to identify the CCHCR1 gene as one of the causative genes by genome analysis. In this study, we created CCHCR1-deficient mice using Cre/loxP technology and confirmed that 25% of CCHCR1-deficient mice that underwent the WAS test for psychological stimulation developed hair loss similar to that observed in human alopecia areata. This suggests that the CCHCR1 gene is a disease susceptibility gene for alopecia areata.