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Birth Defects Res. 2018 Mar 15;110(5):443-455. doi: 10.1002/bdr2.1183. Epub 2018 Jan 8.

Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development.

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Genetics and Genomic Medicine, UCL Institute of Child Health, London, United Kingdom.
GMGF, Aix Marseille University, INSERM, UMR_S910, Marseille, France.
Birth Defects Research Centre, UCL Institute of Child Health, London, United Kingdom.
Department of Paediatric Dermatology, Great Ormond Street Hospital for Children, London, United Kingdom.



MC1R, a G-protein coupled receptor with high affinity for alpha-melanocyte stimulating hormone (αMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk. MC1R mutations affecting human skin and hair color also have pleiotropic effects on the immune response and analgesia. Variants affecting human pigmentation in utero alter the congenital phenotype of both oculocutaneous albinism and congenital melanocytic naevi, and have a possible effect on birthweight.


By in situ hybridization, RT-PCR and immunohistochemistry, we show that MC1R is widely expressed during human, chick and mouse embryonic and fetal stages in many somatic tissues, particularly in the musculoskeletal and nervous systems, and conserved across evolution in these three amniotes. Its dynamic pattern differs from that of TUBB3, a gene overlapping the same locus in humans and encoding class III β-tubulin. The αMSH peptide and the transcript for its precursor, pro-opiomelanocortin (POMC), are similarly present in numerous extra-cutaneous tissues. MC1R genotyping of variants p.(V60M) and p.(R151C) was undertaken for 867 healthy children from the Avon Longitudinal Study of Parent and Children (ALSPAC) cohort, and birthweight modeled using multiple logistic regression analysis. A significant positive association initially found between R151C and birth weight, independent of known birth weight modifiers, was not reproduced when combined with data from an independent genome-wide association study of 6,459 additional members of the same cohort.


These data clearly show a new and hitherto unsuspected role for MC1R in noncutaneous solid tissues before birth.


brain; genetics; heart; hormone; liver; melanocortin; nevus; pomc; prenatal; skin

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