A SINGLE BASE INSERTION IN THE PUTATIVE TRANSMEMBRANE DOMAIN OF THE TYROSINASE GENE AS A CAUSE FOR TYROSINASE-NEGATIVE OCULOCUTANEOUS ALBINISM

被引:44
作者
CHINTAMANENI, CD
HALABAN, R
KOBAYASHI, Y
WITKOP, CJ
KWON, BS
机构
[1] INDIANA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,INDIANAPOLIS,IN 46202
[2] INDIANA UNIV,SCH MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202
[3] YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510
[4] UNIV MINNESOTA,DEPT ORAL PATHOL & GENET,MINNEAPOLIS,MN 55455
关键词
HUMAN ALBINISM; SKIN PIGMENTATION; INSERTIONAL MUTATION; PRENATAL DIAGNOSIS; MELANOCYTE CULTURE;
D O I
10.1073/pnas.88.12.5272
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have determined a molecular defect to be the likely basis for inactivity of the tyrosinase (EC 1.14.18.1) from a patient with tyrosinase-negative oculocutaneous albinism. A single base (thymine) was inserted in exon 5 of the tyrosinase gene following codon 471 in the putative transmembrane coding region. This insertion caused a shift in the reading frame of 19 amino acids at the 3' end and introduced a premature termination signal that would be expected to truncate the protein by 21 amino acids at the carboxyl terminus. The albino tyrosinase was not recognized by antibodies directed to the carboxyl terminus of tyrosinase. Furthermore, as shown by gel electrophoresis of the immunoprecipitated protein, the tyrosinase was almost-equal-to 3 kDa smaller than normal. Similar immunoprecipitation data were obtained when cloned normal and mutant tyrosinases were expressed in COS-1 cells.
引用
收藏
页码:5272 / 5276
页数:5
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