Alopecia Areata Susceptibility Variant Identified by MHC Risk Haplotype Sequencing Reproduces Symptomatic Patched Hair Loss in Mice

April 2018 in “ bioRxiv (Cold Spring Harbor Laboratory) ”

Akira Oka, Atsushi Takagi, Etsuko Komiyama, Shuhei Mano, Kazuyoshi Hosomichi, Shingo Suzuki, Nami Motosugi, Tomomi Hatanaka, Minoru Kimura, Mahoko Takahashi Ueda, So Nakagawa, Hiromi Miura, Masato Ohtsuka, Yuko Haida, Masayuki Tanaka, Tomoyoshi Komiyama, Asako Otomo, Shinji Hadano, Tomotaka Mabuchi, Stephan Beck, Hidetoshi Inoko, Shigaku Ikeda

alopecia areata MHC risk haplotype CCHCR1 gene CRISPR/Cas9 patched hair loss keratin keratin-associated proteins hair shafts hair cuticles keratinization autoimmune factors AA CRISPR

Researchers identified a variant (rs142986308, p.Arg587Trp) in the CCHCR1 gene within the MHC risk haplotype associated with alopecia areata (AA). Using CRISPR/Cas9, they engineered mice to carry this risk allele, which resulted in patched hair loss similar to AA symptoms. Skin biopsies from these mice showed up-regulation of hair-related genes, including keratin and keratin-associated proteins. Transcriptomics revealed CCHCR1 as a novel component of hair shafts and cuticles, suggesting that aberrant keratinization might be an alternative mechanism for AA, alongside known autoimmune factors.

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