Characterization of Ets-1 deficiency-induced depigmentation in a mouse model: insights into vitiligo pathogenesis

Vitiligo is a skin disorder characterized by the loss of melanocytes (MCs), leading to depigmentation. While the exact mechanisms are unclear, the transcription factor Ets-1, known for its role in regulating matrix metalloproteinase expression and MC migration, is suspected to play a part. Ets-1 gene-deficient mice exhibit a vitiligo-like phenotype with spontaneous skin depigmentation, suggesting a direct link between Ets-1 deficiency and MC dysfunction. This study aimed to characterize the molecular and histological features of Ets-1 gene knockout (KO) mice to understand the underlying mechanisms of this depigmentation. Transcriptomic analysis of depigmented and normal skin from Ets-1 KO and wild-type mice revealed significant differentially expressed genes (DEGs). KEGG pathway enrichment analysis demonstrated alterations in metabolic and signal transduction pathways, notably the downregulation of melanogenesis-related genes. RT-qPCR and immunohistochemistry confirmed reduced tyrosinase expression at both transcript and protein levels in the depigmented skin of KO mice. Protein-protein interaction network analysis of the DEGs highlighted a central network involving keratin proteins and discrete interactions regulating melanogenesis, stress response, and cellular signaling pathways. These findings demonstrate that Ets-1 deficiency in mice leads to significant molecular and histological changes consistent with MC dysfunction and depigmentation. The observed downregulation of melanogenesis-related genes and alterations in key signaling pathways provide valuable insights into the molecular basis of Ets-1’s role in MC maintenance and suggest potential therapeutic targets for skin pigmentation disorders, including vitiligo.

• Publication year

  2025

• Venue

  Laboratory Animal Research

• Publication date

  2025-11-28

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1186/s42826-025-00260-8PMID 41310821PMCID 12661662
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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