Affiliation:
1. Genomics, Development and Disease Section, Genetic Disease Research Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA
2. Embryonic Stem Cell and Transgenic Mouse Core, National Human Genome Research Institute National Institutes of Health Bethesda Maryland USA
Abstract
AbstractMFSD12 functions as a transmembrane protein required for import of cysteine into melanosomes and lysosomes. The MFSD12 locus has been associated with phenotypic variation in skin color across African, Latin American, and East Asian populations. The frequency of a particular MFSD12 coding variant, rs2240751 (MAF = 0.08), has been reported to correlate with solar radiation and occur at highest frequency in Peruvian (PEL MAF = 0.48) and Han Chinese (CHB MAF = 0.40) populations, suggesting it could be causative for associated phenotypic variation in skin color. We have generated a mouse knock‐in allele, Mfsd12Y182H, to model the human missense p.Tyr182His human variant. We demonstrate that the variant transcript is stably expressed and that agouti mice homozygote for the variant allele are viable with an altered coat color. This in vivo data confirms that the MFSD12 p.Tyr182His variant functions as a hypomorphic allele sufficient to alter mammalian pigmentation.
Subject
Dermatology,General Biochemistry, Genetics and Molecular Biology,Oncology