# Full length transcriptomic profiling reveals insights into the white coat phenotype in Waardenburg syndrome mice harboring the Mitf R324del mutation

## TL;DR

This study explores how gene expression and alternative splicing contribute to pigmentation defects in mice with a Mitf mutation linked to Waardenburg syndrome.

## Contribution

The study provides new insights into the role of alternative splicing and gene expression in pigmentation defects caused by the Mitf R324del mutation.

## Key findings

- 3619 differentially expressed genes were identified in Mitf mutant mice skin.
- Extensive alternative splicing events were observed, potentially affecting pigment distribution.
- Downregulation of Dct, Mlana, and Snai2 suggests disruption in melanocyte development and melanin biosynthesis.

## 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.

The online version contains supplementary material available at 10.1038/s41598-025-13359-8.