Nature Genetics
20, 244 - 250 (1998)
doi:10.1038/3049
Positional cloning of the zebrafish sauternes gene: a model for
congenital sideroblastic anaemiaAlison Brownlie1, Adriana Donovan1, Stephen J. Pratt1, Barry H. Paw1, 2, Andrew C. Oates3, Carlo Brugnara1, H. Ewa Witkowska4, Shigeru Sassa5
& Leonard I. Zon1, 21
Division of Hematology/Oncology, Children's Hospital, Department of Pediatrics, Harvard Medical School,Boston, Massachusetts, 02115, USA. 2
Howard Hughes Medical Institute, Boston, Massachusetts, 02115, USA. 3
Ludwig Institute for Cancer Research, PO Royal Melbourne Hospital, VIC, Australia. 4
Children's Hospital Oakland Research Institute, Oakland, California 94609, USA. 5
The Rockefeller University, New York, New York 10021, USA.
Correspondence should be addressed to Leonard I. Zon zon@rascal.med.harvard.eduMany 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  -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.
|
