A mutation in the gene for delta-aminolevulinic acid dehydratase (ALAD) causes hypochromic anemia in the medaka, Oryzias latipes.
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.
Sakamoto
Daigo
D
Department of Biological Information, Tokyo Institute of Technology, Nagatsuta, Midori-ku, Yokohama 226-8501, Japan.
Kudo
Hisaaki
H
Inohaya
Keiji
K
Yokoi
Hayato
H
Narita
Takanori
T
Naruse
Kiyoshi
K
Mitani
Hiroshi
H
Araki
Kazuo
K
Shima
Akihiro
A
Ishikawa
Yuji
Y
Imai
Yoshiyuki
Y
Kudo
Akira
A
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
D000623:Porphobilinogen Synthase