POSITIONAL CLONING OF THE ZEBRAFISH SAUTERNES GENE - A MODEL FOR CONGENITAL SIDEROBLASTIC ANEMIA

Many human anaemias are caused by defects in haemoglobin synthesis. Th e zebrafish mutant sauternes (sau) has a microcytic, hypochromic anaem ia, suggesting that haemoglobin production is perturbed. During embryo genesis, sau mutants have delayed erythroid maturation and abnormal gl obin gene expression. Using positional cloning techniques, we show tha t sau encodes the erythroid-specific isoform of delta-aminolevulinate synthase (ALAS2; also known as ALAS-E), the enzyme required for the fi rst step in haem biosynthesis. As mutations in ALAS2 cause congenital sideroblastic anaemia (CSA) in humans, sau represents the first animal model of this disease.