Medaka mutants of organogenesis : an animal model for human diseases

我们筛选了medaka， Oryzias latipes中器官发生缺陷的突变体。用乙基亚硝基脲（ENU）诱变雄性，我们发现突变体在血细胞和各种器官（包括心脏、血管、耳朵和鳍）的发育中存在缺陷。幼虫用茜素红染色，分离出骨突变体。最后，我们建立了53个影响器官发生的突变，其中一些突变表现出一种在斑马鱼中未被描述的独特表型。在建立了20个突变体克隆后，我们开始了突变体的定位克隆和鉴定，并获得了几个候选基因。为了鉴定，我们建立了针对骨和血管的GFP转基因系，并与突变克隆进行杂交，分析其缺陷。□-氨基乙酰丙酸脱水酶（ALAD）基因的突变引起了一种低色素贫血突变体，怀特怀特（who），它表现出血细胞的细长形态和血红蛋白的活性。另一种突变体，非延伸鳍（unextended fin, ufi），表现出鳍延伸缺陷，导致鳍缩小和变短，是由hoxb8基因突变引起的，表现出非规范的wnt通路缺陷。Medaka突变体可能代表了人类疾病的模型。

We have screened for mutants defective in organogenesis in the medaka, Oryzias latipes. Males were mutagenized with ethylnitrosourea (ENU), and we identified mutants that were defective in the development of blood cells and various organs, including heart, blood vessels, ear, and fins. In addition, larvae were stained with alizarin red, and we isolated bone mutants. Finally we established 53 mutations affecting organogenesis, and some mutants exhibited a unique phenotype that has not been described in zebrafish. After establishing selected 20 mutant clones, we have started the positional cloning and characterization of mutants, and several candidate genes are available. For characterization, GFP transgenic lines specific for bone and blood vessel have been established, and then were mated with mutant clones to analyze their defects. A hypochromic anemia mutant, whiteout (who), that shows an elongated morphology of blood cells and little hemoglobin activity, was caused by a mutation in the gene for □-aminolevulinic acid dehydratase (ALAD). Another mutant, unextended fin (ufi), which shows the defect of fin extension resulting a shrunken and short fin, was caused by a mutation in the gene for hoxb8, displaying non-canonical wnt pathway defects. Medaka mutants possibly represent models for the human diseases.