PUBLICATION
Loss-of-function mutations in the melanocortin-2-receptor (mc2r) lead to skin hyperpigmentation in teleost fish
- Authors
- Barreiro-Docío, E., Guerrero-Peña, L., Soni, P., Méndez-Martínez, L., Costas-Prado, C., Alvarado, M.V., Vázquez, J.A., Tort, L., Cerdá-Reverter, J.M., Rotllant, J.
- ID
- ZDB-PUB-260205-11
- Date
- 2026
- Source
- Scientific Reports : (Journal)
- Registered Authors
- Cerdá-Reverter, José Miguel, Rotllant, Josep
- Keywords
- Knockout, Mc2r, Melanocortin, Pigmentation, Steroidogenesis, Zebrafish
- Datasets
- GEO:GSE292242
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems
- Hyperpigmentation*/genetics
- Hyperpigmentation*/metabolism
- Loss of Function Mutation*
- Melanins/biosynthesis
- Melanophores/metabolism
- Receptor, Melanocortin, Type 2*/genetics
- Receptor, Melanocortin, Type 2*/metabolism
- Skin Pigmentation*/genetics
- Zebrafish*/genetics
- Zebrafish*/metabolism
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- PubMed
- 41639367 Full text @ Sci. Rep.
Citation
Barreiro-Docío, E., Guerrero-Peña, L., Soni, P., Méndez-Martínez, L., Costas-Prado, C., Alvarado, M.V., Vázquez, J.A., Tort, L., Cerdá-Reverter, J.M., Rotllant, J. (2026) Loss-of-function mutations in the melanocortin-2-receptor (mc2r) lead to skin hyperpigmentation in teleost fish. Scientific Reports. :.
Abstract
Melanocortins regulate pigmentation via melanocortin receptors (MCRs), which are highly conserved across vertebrates. Unlike other MCRs, the melanocortin 2 receptor (MC2R) is exclusively activated by ACTH; however, its role in pigmentation remains unclear. Using CRISPR/Cas9-generated mc2r knockout zebrafish, we demonstrated that the loss of mc2r in zebrafish results in impaired interrenal steroidogenesis and pronounced hyperpigmentation characterized by an increased number of melanophores and xanthophores while preserving normal patterning. Transcriptomic analyses revealed the upregulation of genes involved in melanosome formation, melanin synthesis, lipid metabolism, and carotenoid accumulation. These findings demonstrate that, in addition to controlling steroidogenesis, mc2r plays a key role in pigment cell development and metabolic regulation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping