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.

我们已经筛选了Medaka（Oryzias latipes）中器官发生缺陷的突变体。雄性用乙硝基环（ENU）诱变，我们确定了在血细胞和各种器官（包括心脏，血管，耳朵，耳朵和鳍）中发育中有缺陷的突变体。另外，将幼虫用艾他林红色染色，我们分离了骨突变体。最后，我们建立了53种影响器官发生的突变，一些突变体暴露了斑马鱼中未描述的独特表型。建立了选定的20个突变克隆后，我们开始了突变体的位置克隆和表征，并且可以使用几个候选基因。为了表征，已经建立了针对骨和血管的GFP转基因线，然后是与突变克隆的伴侣，以分析其缺陷。低色素性贫血突变体（WHO）显示出血细胞的细长形态和几乎没有血红蛋白活性，是由基因中的突变引起的□ - 氨基苯甲酸脱氢酶（ALAD）。另一个突变体，意外的FIN（UFI）显示了FIN扩展的缺陷，导致缩小和短鳍，是由HOXB8基因突变引起的，显示了非基本的Wnt Wnt途径缺陷。 Medaka突变体可能代表人类疾病的模型。