Loss of function mutations of the human melanocortin 1 receptor are commonand are associated with red hair

The melanocortin 1 receptor is a G-protein-coupled receptor that acts as a control point for control of the eumelanin/phaeomelanin ratio in mouse hair . MC1 receptor loss of function function mutations lead to an increase in t he ratio of phaeomelanin/eumelanin in many mammals resulting in yellow or r ed coat colours. We have previously shown that several common point mutatio ns in the human MC1 receptor are overrepresented in North European redheads and in individuals with pale skin, In order to determine the functional si gnificance of these changes we have carried out transfection and binding st udies. Expression of the Val60Leu, Arg142His, Arg151Cys, Arg160Trp, and Asp 294His receptors in COS 1 cells revealed that these receptors were unable t o stimulate cAMP production as strongly as the wild type receptor in respon se to alpha-melanocyte-stimulating hormone stimulation, None of the mutant receptors displayed complete loss of alpha MSH binding, with only the Arg14 2His and Asp294His displaying a slight reduction in binding affinity. (C) 1 999 Academic Press.