Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria
Mutations affecting liver development and function in Medaka, Oryzias latipes, screened by multiple criteria
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DOI：
10.1016/j.mod.2004.04.004
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发表时间：
2004-07-01
影响因子：
2.6
通讯作者：
Furutani-Seiki, M
中科院分区：
文献类型：
--
作者：
Watanabe, T;Asaka, S;Furutani-Seiki, M
我们在这里报告的突变影响肝脏发育和功能的各个方面，在青鳉的系统性诱变筛选的多个测定确定。22个隐性突变分配到19个互补组落入5个表型组。第1组，显示有缺陷的肝脏形态发生，包括四个基因的突变，这可能涉及肠道内胚层的生长或模式的调节。第2组包括影响肝脏偏侧性的三个基因的突变;在该组的kendama突变体中，心脏和肝脏的偏侧性是解耦和随机的。第3组包括改变胆汁颜色的三个基因突变，表明血红蛋白-胆红素代谢和珠蛋白合成缺陷。第4组由三个基因突变组成，其特征是磷脂酶A（2）底物PED 6在胆囊中的荧光代谢产物积累减少。脂质代谢或脂质代谢物的转运可能受到这些突变的影响。组3和组4中的突变可为相关人类疾病提供动物模型。6个基因中的第5组突变影响内胚层、内胚层杆和肝芽的形成，肝脏从这些形成。通过形态学和代谢物标记物筛选鉴定的这些青花菜突变应该为理解功能性肝脏形成的分子机制提供线索。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
We report here mutations affecting various aspects of liver development and function identified by multiple assays in a systematic mutagenesis screen in Medaka. The 22 identified recessive mutations assigned to 19 complementation groups fell into five phenotypic groups. Group 1, showing defective liver morphogenesis, comprises mutations in four genes, which may be involved in the regulation of growth or patterning of the gut endoderm. Group 2 comprises mutations in three genes that affect the laterality of the liver; in kendama mutants of this group, the laterality of the heart and liver is uncoupled and randomized. Group 3 includes mutations in three genes altering bile color, indicative of defects in hemoglobin-bilirubin metabolism and globin synthesis. Group 4 consists of mutations in three genes, characterized by a decrease in the accumulation of fluorescent metabolite of a phospholipase A(2) substrate, PED6, in the gall bladder. Lipid metabolism or the transport of lipid metabolites may be affected by these mutations. Mutations in Groups 3 and 4 may provide animal models for relevant human diseases. Group 5 mutations in six genes affect the formation of endoderm, endodermal rods and hepatic bud from which the liver develops. These Medaka mutations, identified by morphological and metabolite marker screens, should provide clues to understanding molecular mechanisms underlying formation of a functional liver. (C) 2004 Elsevier Ireland Ltd. All rights reserved.