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A Dominant Mutation in Gαs-Protein Increases Hair Pigmentation

Goff, PS; Budd, P; Logan, DW; Keighren, M; Cantero, M; McKie, L; Montoliu, L; Jackson, IJ; Sviderskaya, EV (2025) A Dominant Mutation in Gαs-Protein Increases Hair Pigmentation. Pigment Cell & Melanoma Research, 38 (3). e70025. ISSN 1755-1471 https://doi.org/10.1111/pcmr.70025
SGUL Authors: Sviderskaya, Elena Vladimirovna

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Abstract

We have identified a chemically induced mouse mutation which increases the eumelanic hair pigmentation. We identify a coding mutation, A3533G, resulting in an amino acid substitution Y1133C, in the Gnas gene encoding the Gαs subunit of the tripartite G‐protein, consistent with an activation of signalling via MC1R. In addition heterozygous mutant females are significantly lighter than wild type littermates. In cultured melanocytes, derived from mutant mice crossed to C57BL6 mice carrying Cdkn2atm1Rdp, basal pigmentation is higher than wild type melanocytes derived from litter mates. However, the addition of exogenous NDP‐MSH does not increase pigmentation in mutant melanocytes in contrast to the pigmentation response of non‐mutant melanocytes. The mutant and wild type cells respond in the same way to agouti signalling protein (ASP), consistent with ASP signalling mediated through a pathway other than Gαs‐protein.

Item Type: Article
Additional Information: © 2025 The Author(s). Pigment Cell & Melanoma Research published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
SGUL Research Institute / Research Centre: Academic Structure > Neuroscience & Cell Biology Research Institute
Academic Structure > Neuroscience & Cell Biology Research Institute > Molecular & Cellular Sciences
Journal or Publication Title: Pigment Cell & Melanoma Research
ISSN: 1755-1471
Language: en
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
MC_UU_00007/4Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
108429/Z/15/ZWellcome Trusthttp://dx.doi.org/10.13039/100004440
PID2021-127644OB-I00Spanish Ministry of Science and InnovationUNSPECIFIED
URI: https://openaccess.sgul.ac.uk/id/eprint/117501
Publisher's version: https://doi.org/10.1111/pcmr.70025

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