1990 Fiscal Year Final Research Report Summary
Molecular Genetics of Human Albinism
| Project/Area Number |
63480471
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human genetics
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| Research Institution | Tohoku University |
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Principal Investigator |
KIKUCHI Hideaki Tohoku Univ. Res. Inst. Tb & Cancer Associate Prof, 抗酸菌病研究所, 助教授 (60006111)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hiroaki Tohoku Univ. Facul. Science Assistant Prof., 理学部, 助手 (40174809)
TAKEUCHI Takuji Tohoku Univ. Facul. Science Professor, 理学部, 教授 (60006426)
ISHIGURO Sei-ichi Tohoku Univ. Medical School Lecturer, 医学部, 構師 (20111271)
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| Project Period (FY) |
1988 – 1990
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| Keywords | ALBINISM / TYROSINASE / TRANSGENIC MOUSE |
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| Research Abstract |
1. A human tyrosinase gene containing a 5'-flanking region and the first exon was isolated from a normal human liver library using mouse tyrosinase cDNA as a probe for screening. In the 5'-upstream region of transcription start sites, there is a putative TATA box and CAAT box and some palindromic sequences.
2. Enzymatic DNA amplification and direct DNA sequencing were used to detect a mutation in the tyrosinase gene of a Japanese patient with tyrosinase-negative albinism. Single-base change could be detected by direct sequencing. This base change (G to A) is thought to result in an amino acid change (A
rg to Gln) in tyrosinase of the patient. The mutant allele can be also identified by Southem blot hybridization using MspI because the change destroys the MspI site.
3. We introduced a human-mouse fused minigene, hg-tyrs-J, in which the human genomic 5' non-coding flanking sequence was fused to a mouse tyrosinase cDNA, into fertilized eggs of albino mice. We obtained two pigmented mice and established some transgenic lines. Histological analysis revealed that melanization was restricted to melanocytes in hair bulbs and eyes in transgenic mice. These results suggested that this minigene encodes active throsinase protein and that its 5'-flanking region contains the regulatory sequences for the expression and that there is a common or very similar mechanism between mice and humans in tyrosinase gene regulation.
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Research Products
(20 results)
