Originally published as Genetics Published Articles Ahead of Print on February 1, 2008.

Genetics, Vol. 178, 761-769, February 2008, Copyright © 2008
doi:10.1534/genetics.107.073387

Rescue From Oculocutaneous Albinism Type 4 Using Medaka slc45a2 cDNA Driven by Its Own Promoter

Shoji Fukamachi*,{dagger},1, Masato Kinoshita{ddagger}, Taro Tsujimura*, Atsuko Shimada§, Shoji Oda*, Akihiro Shima§, Axel Meyer{dagger}, Shoji Kawamura* and Hiroshi Mitani*

* Department of Integrated Biosciences, University of Tokyo, Kashiwa-no-ha, Kashiwa-shi, Chiba 277-8562, Japan, {dagger} Department of Biology, University of Konstanz, D-78457 Konstanz, Germany, {ddagger} Division of Applied Biosciences, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan and § Department of Biological Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

1 Corresponding author: Lehrstuhl für Zoologie und Evolutionsbiologie, Department of Biology, University of Konstanz, D-78457 Konstanz, Germany.
E-mail: shoji.fukamachi{at}uni-konstanz.de

Patients and vertebrate mutants with oculocutaneous albinism type 4 (OCA4) have mutations in the solute carrier family 45 member 2 (slc45a2) gene. However, there is no empirical evidence for this gene–phenotype relationship. There is a unique OCA4 mutant in medaka (b) that exhibits albinism only in the skin, but the mechanism underlying this phenotype is also unknown. In this study, we rescued medaka OCA4 phenotypes, in both the eyes and the skin, by micro-injection of an slc45a2-containing genomic fragment or slc45a2 cDNA driven by its own 0.9-kb promoter. We also identified a spontaneous nucleotide change of 339 bp in the promoter as the b mutation. There are multiple transcription start sites in medaka slc45a2, as in its human ortholog, and only the shortest and eye-specific mRNA is transcribed with the b mutation. Interestingly, we further revealed a conserved pyrimidine (Py)-rich sequence of ~10 bp in the promoter by medaka–pufferfish comparative genomics and verified that it plays an indispensable role for expression of slc45a2 in the skin. Further studies of the 0.9-kb promoter identified in this study should provide insights into the cis/trans-regulatory mechanisms underlying the ocular and cutaneous expression of slc45a2.