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Medaka mutants of organogenesis : an animal model for human diseases

器官发生的青鳉突变体：人类疾病的动物模型

基本信息

批准号：
17370078
负责人：
KUDO Akira
金额：
$ 8.13万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17370078/
关键词：
medaka mutant positional cloning bone heart fin human diseases animal model

项目摘要

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.

我们筛选了青鳉器官发生缺陷的突变体。用乙基亚硝基脲（ENU）对雄性进行诱变，我们发现了血细胞和各种器官（包括心脏、血管、耳朵和鳍）发育缺陷的突变体。此外，幼虫用茜素红染色，我们分离出骨突变体。最后，我们建立了53个影响器官发生的突变，一些突变体表现出独特的表型，尚未在斑马鱼中描述。在建立了选定的20个突变体克隆后，我们已经开始了突变体的定位克隆和表征，并获得了几个候选基因。为了表征，已经建立了对骨和血管特异的GFP转基因株系，然后与突变克隆交配以分析其缺陷。一种低色素性贫血突变体，whiteout（who），表现出血细胞的细长形态和血红蛋白活性很低，是由□-氨基乙酰丙酸脱氢酶（ALAD）基因突变引起的。另一个突变体，unextended fin（ufi），表现出鳍延伸缺陷导致的收缩和短鳍，是由hoxb 8基因突变引起的，表现出非典型的wnt途径缺陷。青鳉突变体可能代表了人类疾病的模型。