Functional analysis of OCA4 mutant sequences using under white mouse melanocytes

• Project/Area Number: 25860932
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Dermatology
• Research Institution: Yamagata University
• Principal Investigator: KONNO TAKAYUKI 山形大学, 医学部, 助教 (00359564)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 眼皮膚白皮症 / 遺伝子 / 機能解析 / OCA4 / 電子顕微鏡的観察 / タンパク量の比較 / SLC45A2タンパク / 変異導入 / 電子顕微鏡

Outline of Final Research Achievements

Oculocutaneous albinism Type IV (OCA4) is the result of single gene mutation in Solute Carrier Family 45，member 2 gene（SLC45A2）.The clinical phenotypes of OCA4 patients vary depending on their mutant genotypes. Two of these mutations，the p.D157N and the p.G188V alleles，were the first and second most frequently found variants in Japanese patients.I investigated the differential complementation of defective melanin biosynthesis and the hypopigmentation in melanocytes (under white cells; uw) established from an OCA4 mouse model by transfection with wild and mutant human SLC45A2 cDNA sequences. Over-expression of normal human SLC45A2 protein in uw cells restored melanin production, while the p.D157N-mutant,P.G188V-mutant protein failed.