Abstract
BackgroundMC1R, 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.Methods and ResultsBy 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.ConclusionsThese data clearly show a new and hitherto unsuspected role for MC1R in noncutaneous solid tissues before birth.
Highlights
MC1R, a G-protein coupled receptor with high affinity for alphamelanocyte stimulating hormone, modulates pigment production in melanocytes from many species and is associated with human melanoma risk
In order to establish whether Mc1r is likely to be activated before birth by specific ligand-dependent binding, we examined the transcription of Pomc during mouse and chicken embryogenesis by in situ hybridization
We found that of 270 normal children from the English Avon Longitudinal Study of Parent and Children (ALSPAC) study (Jones et al, 2000), 42 carried at least one R151C variant and 39 at least one V92M variant of MC1R
Summary
MC1R, a G-protein coupled receptor with high affinity for alphamelanocyte stimulating hormone (aMSH), modulates pigment production in melanocytes from many species and is associated with human melanoma risk. MC1R mutations affecting human skin and hair color 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
