Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation
Abstract Waardenburg syndrome (WS) is distinguished by depigmented patches of hair and skin, striking blue eyes and sensorineural hearing loss. Studies on alternative splicing (AS) in the abnormal pigmentation in skin in WS are currently poorly understood. In this study, we conducted comprehensive f...
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Nature Portfolio
2025-07-01
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| Online Access: | https://doi.org/10.1038/s41598-025-13359-8 |
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| author | Wei Gong Lu Ma Zhili Feng Xiangyao Zeng Lile Ouyang Yihan Hu Xianlin Liu Jie Wen Xiaoming Kang Yalan Liu Hong Wu Qiancheng Jing Chufeng He Yong Feng |
| author_facet | Wei Gong Lu Ma Zhili Feng Xiangyao Zeng Lile Ouyang Yihan Hu Xianlin Liu Jie Wen Xiaoming Kang Yalan Liu Hong Wu Qiancheng Jing Chufeng He Yong Feng |
| author_sort | Wei Gong |
| collection | DOAJ |
| description | Abstract Waardenburg syndrome (WS) is distinguished by depigmented patches of hair and skin, striking blue eyes and sensorineural hearing loss. Studies on alternative splicing (AS) in the abnormal pigmentation in skin in WS are currently poorly understood. In this study, we conducted comprehensive full-length transcriptome sequencing analysis on abdominal skin tissues from mice harboring the Mitf p.R324del mutation and wild-type controls. Our analysis revealed 3619 differentially expressed genes (DEGs), with 1916 upregulated and 1703 downregulated. Notably, pigment-associated genes and related signaling pathways were significantly enriched. Additionally, we identified extensive AS events in the skin tissue of Mitf mutant mice, including 97 A3, 85 A5, 101 AF, 42 AL, 8 MX, 44 RI, and 184 SE events (P < 0.05), suggesting AS events may contribute to the pigment distribution patterns in Mitf p.R324del mutation mice. Furthermore, we observed downregulation of Dct, Mlana, and Snai2, which indicates that Mitf mutations disrupt neural crest cells into melanocytes, melanosome structure, and melanin biosynthesis. Overall, our results support that variation in gene expression and AS are important and complementary mechanisms governing pigmentation defects in WS. |
| format | Article |
| id | doaj-art-e62d37216aee4d3292d0caf9139ebe49 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-07-01 |
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| spelling | doaj-art-e62d37216aee4d3292d0caf9139ebe492025-08-20T03:43:15ZengNature PortfolioScientific Reports2045-23222025-07-0115111210.1038/s41598-025-13359-8Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutationWei Gong0Lu Ma1Zhili Feng2Xiangyao Zeng3Lile Ouyang4Yihan Hu5Xianlin Liu6Jie Wen7Xiaoming Kang8Yalan Liu9Hong Wu10Qiancheng Jing11Chufeng He12Yong Feng13Department of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaInstitute of Otorhinolaryngology, Head and Neck Surgery, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaInstitute of Otorhinolaryngology, Head and Neck Surgery, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South UniversityDepartment of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South UniversityDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaDepartment of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South UniversityDepartment of Otorhinolaryngology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South ChinaAbstract Waardenburg syndrome (WS) is distinguished by depigmented patches of hair and skin, striking blue eyes and sensorineural hearing loss. Studies on alternative splicing (AS) in the abnormal pigmentation in skin in WS are currently poorly understood. In this study, we conducted comprehensive full-length transcriptome sequencing analysis on abdominal skin tissues from mice harboring the Mitf p.R324del mutation and wild-type controls. Our analysis revealed 3619 differentially expressed genes (DEGs), with 1916 upregulated and 1703 downregulated. Notably, pigment-associated genes and related signaling pathways were significantly enriched. Additionally, we identified extensive AS events in the skin tissue of Mitf mutant mice, including 97 A3, 85 A5, 101 AF, 42 AL, 8 MX, 44 RI, and 184 SE events (P < 0.05), suggesting AS events may contribute to the pigment distribution patterns in Mitf p.R324del mutation mice. Furthermore, we observed downregulation of Dct, Mlana, and Snai2, which indicates that Mitf mutations disrupt neural crest cells into melanocytes, melanosome structure, and melanin biosynthesis. Overall, our results support that variation in gene expression and AS are important and complementary mechanisms governing pigmentation defects in WS.https://doi.org/10.1038/s41598-025-13359-8Full-length transcriptome sequencingWaardenburg syndromeMitfPigmentation |
| spellingShingle | Wei Gong Lu Ma Zhili Feng Xiangyao Zeng Lile Ouyang Yihan Hu Xianlin Liu Jie Wen Xiaoming Kang Yalan Liu Hong Wu Qiancheng Jing Chufeng He Yong Feng Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation Scientific Reports Full-length transcriptome sequencing Waardenburg syndrome Mitf Pigmentation |
| title | Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation |
| title_full | Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation |
| title_fullStr | Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation |
| title_full_unstemmed | Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation |
| title_short | Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation |
| title_sort | full length transcriptomic profiling reveals insights into the white coat phenotype in waardenburg syndrome mice harboring the mitf r324del mutation |
| topic | Full-length transcriptome sequencing Waardenburg syndrome Mitf Pigmentation |
| url | https://doi.org/10.1038/s41598-025-13359-8 |
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