Search

Your search keyword '"Asako Otomo"' showing total 2 results
Start Over Author "Asako Otomo" Journal ebiomedicine
2 results on '"Asako Otomo"'

1. Alopecia areata susceptibility variant in MHC region impacts expressions of genes contributing to hair keratinization and is involved in hair loss

Author

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

Subjects
Alopecia areata, CRISPR/Cas9, MHC, Haplotype, Association, Sequencing, Medicine, Medicine (General), R5-920
Abstract

ABSTRACT: Background: Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods: We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings: We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation: Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. Funding: This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).

Published
2020
Full Text
View/download PDF

2. Alopecia areata susceptibility variant in MHC region impacts expressions of genes contributing to hair keratinization and is involved in hair loss

Author

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

Subjects
0301 basic medicine, Research paper, T-Lymphocytes, lcsh:Medicine, Hair keratin, Major Histocompatibility Complex, Mice, 0302 clinical medicine, Keratins, Hair-Specific, Keratin, Haplotype, Sequencing, Genetics, chemistry.chemical_classification, lcsh:R5-920, Genome, biology, integumentary system, Intracellular Signaling Peptides and Proteins, General Medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Keratins, lcsh:Medicine (General), Hair Follicle, Alopecia Areata, Major histocompatibility complex, General Biochemistry, Genetics and Molecular Biology, Autoimmune Diseases, Association, 03 medical and health sciences, medicine, Animals, Humans, Genetic Predisposition to Disease, Gene, CRISPR/Cas9, Alleles, lcsh:R, Alopecia areata, medicine.disease, Hair follicle, Disease Models, Animal, 030104 developmental biology, Hair loss, chemistry, Haplotypes, biology.protein, MHC, Carrier Proteins, Hair
Abstract

Background Alopecia areata (AA) is considered a highly heritable, T-cell-mediated autoimmune disease of the hair follicle. However, no convincing susceptibility gene has yet been pinpointed in the major histocompatibility complex (MHC), a genome region known to be associated with AA as compared to other regions. Methods We engineered mice carrying AA risk allele identified by haplotype sequencing for the MHC region using allele-specific genome editing with the CRISPR/Cas9 system. Finally, we performed functional evaluations in the mice and AA patients with and without the risk allele. Findings We identified a variant (rs142986308, p.Arg587Trp) in the coiled-coil alpha-helical rod protein 1 (CCHCR1) gene as the only non-synonymous variant in the AA risk haplotype. Furthermore, mice engineered to carry the risk allele displayed a hair loss phenotype. Transcriptomics further identified CCHCR1 as a novel component interacting with hair cortex keratin in hair shafts. Both, these alopecic mice and AA patients with the risk allele displayed morphologically impaired hair and comparable differential expression of hair-related genes, including hair keratin and keratin-associated proteins (KRTAPs). Interpretation Our results implicate CCHCR1 with the risk allele in a previously unidentified subtype of AA based on aberrant keratinization in addition to autoimmune events. Funding This work was supported by JSPS KAKENHI (JP16K10177) and the NIHR UCLH Biomedical Research center (BRC84/CN/SB/5984).

Published
2020

Catalog

Books, media, physical & digital resources
See catalog results