Positional cloning of the zebrafish sauternes gene:: a model for congenital sideroblastic anaemia
Positional cloning of the zebrafish sauternes gene:: a model for congenital sideroblastic anaemia
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DOI：
10.1038/3049
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发表时间：
1998-11-01
期刊：
影响因子：
30.8
通讯作者：
Zon, LI
中科院分区：
文献类型：
--
作者：
Brownlie, A;Donovan, A;Zon, LI
许多人类贫血是由于血红蛋白合成缺陷引起的。斑马鱼突变体sauternes（sau）有一种小细胞低色素性贫血，表明血红蛋白的产生受到干扰。在胚胎发生过程中，sau突变体具有延迟的红系成熟和异常的珠蛋白基因表达。使用定位克隆技术，我们表明，sau编码红细胞特异性亚型的δ-氨基乙酰丙酸合酶（ALAS 2，也称为ALAS-E），所需的血红素生物合成的第一步的酶。由于ALAS 2突变导致人类先天性铁粒幼细胞贫血（CSA），因此sau是该疾病的第一个动物模型。
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.