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.