title: A mutation in the gene for delta-aminolevulinic acid dehydratase (ALAD) causes hypochromic anemia in the medaka, Oryzias latipes.
abstract: A genetic screen for mutations affecting embryogenesis in the medaka, Oryzias latipes, identified a mutant, whiteout (who), that exhibited hypochromic anemia. The who mutant initially had the normal number of blood cells, but it then gradually decreased during the embryonic and larval stages. The blood cells in the who mutants show an elongated morphology and little hemoglobin activity. Genetic mapping localized who to the vicinity of a LG12 marker, olgc1. By utilizing the highly conserved synteny between medaka and pufferfish, we identified a gene for delta-aminolevulinic acid dehydratase (ALAD), which is the second enzyme in the heme synthetic pathway, as a candidate for who. We found a missense mutation in the alad gene that was tightly linked to the who phenotype, strongly suggesting that the hypochromic anemia phenotype in the who mutant is caused by a loss of the alad function. Thus, who mutants represent a model for the human disease ALAD-deficiency porphyria.
authors.affiliation: Department of Biological Information, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
authors.forename: Daigo
authors.initials: D
authors.lastname: Sakamoto
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Kudo
authors.forename: Keiji
authors.initials: K
authors.lastname: Inohaya
authors.forename: Hayato
authors.initials: H
authors.lastname: Yokoi
authors.forename: Takanori
authors.initials: T
authors.lastname: Narita
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Naruse
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Araki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Imai
authors.forename: Akira
authors.initials: A
authors.lastname: Kudo
mesh_terms: D000747:Anemia, Hypochromic / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D002874:Chromosome Mapping; D020869:Gene Expression Profiling; D006321:Heart / Q000196:embryology; D009990:Oryzias / Q000235:genetics* / Q000378:metabolism; D000623:Porphobilinogen Synthase / Q000235:genetics* / Q000378:metabolism; D023741:Takifugu / Q000235:genetics
chemical_list: D000623:Porphobilinogen Synthase