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Relationship between ureteral bud and metanephric mesenchyme in mouse embryo

小鼠胚胎输尿管芽与后肾间质的关系

基本信息

批准号：
11470336
负责人：
KAMOTO Tsohiyuki
金额：
$ 7.17万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Organogenesis of the kidney consists of at least four steps. Step 1 is formation of the metanephric mesenchyme in the intermediate mesoderm and subsequent outgrowth of the ureteric bud from the Wolffian duct. Mutation-induced congenital anomalies are promising tools for investigating critical genetic events in organogenesis. So far several Spontaneous murine models of defects in renal organogenesis have been reported, including Danforth Short Tail (Sd), urogenital syndrome (us) and limb deformity (Id). Furthermore, genetic manipulations have identified a number of genes that affect the organogenesis of the urogenital system. Unlike the anomalies in most other models, the anomaly in FUBI mice is pure renal agenesis without accompanying urogenital or skeletal system malformations FUBI (failure of ureteric bud invasion) is a highly inbred strain of mouse with a high spontaneous incidence of uni- or bilateral renal agenesis (60%). Bilateral renal agenesis is lethal within 2 days after birt … More h. The primary defect of FUBI is failure of the ureteric bud to penetrate into the metanephric mesenchyme at around embryonic day 1 1, resulting in apoptosis of metanephric cells and leading to renal agenesis on the affected side. The metanephros seemed to be normal because co-culturing of the FUBI metanephros with homologous spinal cord induced differentiation of the rudiment, but co-culturing with the homologous ureteric bud frequently did not. Genetic analysis revealed that more than two genes were involved in this malformation and we mapped one of the modifier loci,fubil, on chromosome 2, at 〜65 cM from the centromere. In this region, there are two possible candidate genes, Wilms ' tumor 1 andformin, that play important roles in kidney development. Some offormin mutants shared a similar phenotype with FUBI; however, there was no difference in the expression offormin in embryonic kidneys between FUBI and control NFS/N mice. Studies offubil congenic mice indicated that interaction of two or more loci is essential for the FUBI phenotype Less

肾脏的器官发生至少包括四个步骤。第一步是在中间中胚层形成后肾间充质，然后从沃尔菲管中长出输尿管芽。突变诱导的先天性异常是研究器官发生中的关键遗传事件的很有前途的工具。到目前为止，已经报道了几种自发的小鼠肾脏器官发生缺陷的模型，包括丹佛斯短尾(SD)、泌尿生殖综合征(US)和肢体畸形(ID)。此外，基因操作已经确定了一些影响泌尿生殖系统器官发生的基因。与大多数其他模型中的异常不同，FUBI小鼠的异常是纯肾发育不全，不伴有泌尿生殖系统或骨骼系统畸形。FUBI(输尿管芽侵袭失败)是一种高度近交系小鼠，单侧或双侧肾发育不全的自发性发生率很高(60%)。双侧肾发育不全在BIRT…后2天内死亡FUBI的主要缺陷是在胚胎11天左右输尿管芽未能穿透后肾间充质，导致后肾细胞凋亡，导致患侧肾脏发育不全。后肾似乎是正常的，因为FUBI后肾与同种异体脊髓共培养诱导了雏形的分化，但与同种输尿管芽共培养往往不能。遗传分析表明，不止两个基因参与了这一畸形，我们将其中一个修饰基因fubil定位在距离着丝粒约65 cM的2号染色体上。在这个区域，有两个可能的候选基因，Wilms‘s Tumor 1和Form in，在肾脏发育中发挥重要作用。FUBI小鼠与FUBI小鼠有相似的表型，但在FUBI小鼠和对照组小鼠的肾脏中，FUBI小鼠胚胎肾脏中Forin的表达没有差异。对ubil同源基因小鼠的研究表明，两个或多个基因座的相互作用对FUBI表型较少是必不可少的。