Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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5-Aminolevulinate Synthetase / genetics*
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Amino Acid Sequence
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Anemia, Sideroblastic / congenital
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Anemia, Sideroblastic / enzymology*
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Anemia, Sideroblastic / genetics*
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Animals
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Base Sequence
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Cloning, Molecular
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DNA, Complementary / genetics
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Disease Models, Animal
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Hemoglobins / biosynthesis
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Hemoglobins / genetics
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Humans
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Isoenzymes / genetics*
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Models, Genetic
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Molecular Sequence Data
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Mutation
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Phenotype
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Sequence Homology, Amino Acid
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Zebrafish / genetics*
Substances
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DNA, Complementary
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Hemoglobins
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Isoenzymes
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5-Aminolevulinate Synthetase