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A missense mutation in Lama3 causes androgen alopecia

Hair loss disorders such as androgenetic alopecia have caused serious disturbances to normal human life. Animal models play an important role in exploring pathogenesis of disease and evaluating new therapies. NIH hairless mice are a spontaneous hairless mouse discovered and bred in our laboratory. I...

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Autores principales: Ji, Zhong-Hao, Ren, Wen-Zhi, He, Song, Wu, Hong-Yu, Yuan, Bao, Chen, Jian, Jin, Hong-Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682005/
https://www.ncbi.nlm.nih.gov/pubmed/38012251
http://dx.doi.org/10.1038/s41598-023-48337-5
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author Ji, Zhong-Hao
Ren, Wen-Zhi
He, Song
Wu, Hong-Yu
Yuan, Bao
Chen, Jian
Jin, Hong-Juan
author_facet Ji, Zhong-Hao
Ren, Wen-Zhi
He, Song
Wu, Hong-Yu
Yuan, Bao
Chen, Jian
Jin, Hong-Juan
author_sort Ji, Zhong-Hao
collection PubMed
description Hair loss disorders such as androgenetic alopecia have caused serious disturbances to normal human life. Animal models play an important role in exploring pathogenesis of disease and evaluating new therapies. NIH hairless mice are a spontaneous hairless mouse discovered and bred in our laboratory. In this study, we resequenced the genomes of NIH normal mice and NIH hairless mice and obtained 3,575,560 high-quality, plausible SNP loci and 995,475 InDels. The Euclidean distance algorithm was used to assess the association of SNP loci with the hairless phenotype, at a threshold of 0.62. Two regions of chromosome 18 having the highest association with the phenotype contained 345 genes with a total length of 13.98 Mb. The same algorithm was used to assess the association of InDels with the hairless phenotype at a threshold of 0.54 and revealed a region of 25.45 Mb in length, containing 518 genes. The mutation candidate gene Lama3 (NM_010680.2: c.652C>T; NP_034810.1: p. Arg217Cys) was selected based on the results of functional gene analysis and mutation prediction screening. Lama3 (R217C) mutant mice were further constructed using CRISPR/Cas9 technology, and the relationship between Lama3 point mutations and the hairless phenotype were clarified by phenotypic observation. The results showed that male Lama3 point mutation mice started to lose hair on the 80th day after birth, and the hair loss area gradually expanded over time. H&E staining of skin sections showed that the point mutation mice had increased sebaceous glands in the dermis and missing hair follicle structure (i.e., typical symptoms of androgenetic alopecia). This study is a good extension of the current body of knowledge about the function of Lama3, and the constructed Lama3 (R217C) mutant mice may be a good animal model for studying androgenetic alopecia.
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spelling pubmed-106820052023-11-30 A missense mutation in Lama3 causes androgen alopecia Ji, Zhong-Hao Ren, Wen-Zhi He, Song Wu, Hong-Yu Yuan, Bao Chen, Jian Jin, Hong-Juan Sci Rep Article Hair loss disorders such as androgenetic alopecia have caused serious disturbances to normal human life. Animal models play an important role in exploring pathogenesis of disease and evaluating new therapies. NIH hairless mice are a spontaneous hairless mouse discovered and bred in our laboratory. In this study, we resequenced the genomes of NIH normal mice and NIH hairless mice and obtained 3,575,560 high-quality, plausible SNP loci and 995,475 InDels. The Euclidean distance algorithm was used to assess the association of SNP loci with the hairless phenotype, at a threshold of 0.62. Two regions of chromosome 18 having the highest association with the phenotype contained 345 genes with a total length of 13.98 Mb. The same algorithm was used to assess the association of InDels with the hairless phenotype at a threshold of 0.54 and revealed a region of 25.45 Mb in length, containing 518 genes. The mutation candidate gene Lama3 (NM_010680.2: c.652C>T; NP_034810.1: p. Arg217Cys) was selected based on the results of functional gene analysis and mutation prediction screening. Lama3 (R217C) mutant mice were further constructed using CRISPR/Cas9 technology, and the relationship between Lama3 point mutations and the hairless phenotype were clarified by phenotypic observation. The results showed that male Lama3 point mutation mice started to lose hair on the 80th day after birth, and the hair loss area gradually expanded over time. H&E staining of skin sections showed that the point mutation mice had increased sebaceous glands in the dermis and missing hair follicle structure (i.e., typical symptoms of androgenetic alopecia). This study is a good extension of the current body of knowledge about the function of Lama3, and the constructed Lama3 (R217C) mutant mice may be a good animal model for studying androgenetic alopecia. Nature Publishing Group UK 2023-11-27 /pmc/articles/PMC10682005/ /pubmed/38012251 http://dx.doi.org/10.1038/s41598-023-48337-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Ji, Zhong-Hao
Ren, Wen-Zhi
He, Song
Wu, Hong-Yu
Yuan, Bao
Chen, Jian
Jin, Hong-Juan
A missense mutation in Lama3 causes androgen alopecia
title A missense mutation in Lama3 causes androgen alopecia
title_full A missense mutation in Lama3 causes androgen alopecia
title_fullStr A missense mutation in Lama3 causes androgen alopecia
title_full_unstemmed A missense mutation in Lama3 causes androgen alopecia
title_short A missense mutation in Lama3 causes androgen alopecia
title_sort missense mutation in lama3 causes androgen alopecia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10682005/
https://www.ncbi.nlm.nih.gov/pubmed/38012251
http://dx.doi.org/10.1038/s41598-023-48337-5
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