Effects of G-protein mutations on skin color

Abstract
A new class of dominant dark skin (Dsk) mutations discovered in a screen of ∼30,000 mice is caused by increased dermal melanin. We identified three of four such mutations as hypermorphic alleles of Gnaq and Gna11, which encode widely expressed Gαq subunits, act in an additive and quantitative manner, and require Ednrb. Interactions between Gq and Kit receptor tyrosine kinase signaling can mediate coordinate or independent control of skin and hair color. Our results provide a mechanism that can explain several aspects of human pigmentary variation and show how polymorphism of essential proteins and signaling pathways can affect a single physiologic system.