Brownlie, A., Donovan, A., Pratt, S.J., Paw, B.H., Oates, A.C., Brugnara, C., Witkowska, H.E., Sassa, S., and Zon, L.I. (1998) Positional cloning of the zebrafish sauternes gene: a model for congenital sideroblastic anaemia. Nature Genetics. 20:244-250.
Many human anaemias are caused by defects in haemoglobin synthesis. The zebrafish mutant sauternes (sau) has a microcytic, hypochromic anaemia, suggesting that haemoglobin production is perturbed. During embryogenesis, sau mutants have delayed erythroid maturation and abnormal globin gene expression. Using positional cloning techniques, we show that sau encodes the erythroid-specific isoform of delta-aminolevulinate synthase (ALAS2; also known as ALAS-E), the enzyme required for the first step in haem biosynthesis. As mutations in ALAS2 cause congenital sideroblastic anaemia (CSA) in humans, sau represents the first animal model of this disease.