Abstract：
MFSD12 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.
摘要：
MFSD12用作将半胱氨酸导入黑色素体和溶酶体所需的跨膜蛋白。MFSD12基因座与非洲肤色的表型变异有关，拉丁美洲,和东亚人口。特定MFSD12编码变体的频率，rs2240751(MAF=0.08),据报道，与太阳辐射相关，在秘鲁（PELMAF=0.48）和汉族（CHBMAF=0.40）人群中发生频率最高，这表明它可能是皮肤颜色相关表型变异的原因。我们产生了一个小鼠敲入等位基因,Mfsd12Y182H,模拟人类错觉p.Tyr182他的人类变体。我们证明了变体转录物是稳定表达的，并且变体等位基因的agouti小鼠纯合子具有改变的皮毛颜色。该体内数据证实MFSD12p.Tyr182His变体作为足以改变哺乳动物色素沉着的低态等位基因起作用。
