Lethality of Rw/Rw mouse embryos during early postimplantation development.
Lethality of Rw/Rw mouse embryos during early postimplantation development.
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Rw/Rw 小鼠胚胎在植入后早期发育过程中的致死率。
DOI：
10.1006/dbio.1995.1082
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Lo,CW
中科院分区：
文献类型：
--
作者：
Bucan,M;Nagle,DL;Hough,RB;Chapman,VM;Lo,CW
小鼠中的三种突变，白色斑点(W)，臀部白色（Rw）和斑块（Ph），基于它们密切的遗传连锁和相似的突变表型，被描述为“基因三胞胎”。研究发现，W表型是由改变c-kit原癌基因的突变引起的，Ph值与Pdgfra的缺失有关，这表明可以使用特定的分子试剂来分析第三个突变体“臀部白”的染色体结构。这些研究表明Rw与一个大的染色体反转有关。在这项研究中，我们发现有可能产生Rw染色体特异性的分子标记，因为Rw染色体倒立部分与野生型同源物之间的重组受到抑制。利用一个这样的标记，我们能够对Rw/+杂交后代进行基因分型。这使我们能够证明Rw纯合子胚胎在妊娠9.5天左右死亡。组织学分析显示，胚胎经过原肠胚形成，形成三胚层，在某些情况下，表现出明确的轴向中线和明显的脊索板。然而，突变胚胎明显小于野生型，从第7.5天开始，尺寸差异就很明显，随着发育的进展，差异越来越大。这些形态学数据进一步支持遗传证据，表明Rw突变的发育致死性不是由小鼠5号染色体中心部分rtk簇内基因的破坏引起的。此外，我们提出的证据表明，Kit和Pdgfra在几个成人组织中都是从Rw染色体表达的。这些研究结果表明，鉴定被Rw突变破坏的序列将为进一步了解早期种植后发育的调控提供帮助。
Three mutations in the mouse, white spotting (W), rump white (Rw), and patch (Ph), are described as a "gene triplet" on the basis of their close genetic linkage and similar mutant phenotypes. The finding that the W phenotype results from mutations altering the c-kit protooncogene, and that Ph is associated with the deletion of Pdgfra, suggested specific molecular reagents which could be used for the analysis of the chromosomal structure of the third mutation, rump white. Such studies indicated that Rw is associated with a large chromosomal inversion. In this study, we showed that it is possible to generate molecular markers specific for the Rw chromosome, as recombination is suppressed between the inverted portion of the Rw chromosome and the wild-type homologue. Using one such marker, we were able to genotype the offspring of Rw/+ intercrosses. This enabled us to show that Rw homozygote embryos die around 9.5 days of gestation. Histological analysis revealed that the embryos undergo gastrulation, forming three germ layers, and in some cases, exhibit a defined axial midline with an apparent notochordal plate. However, mutant embryos are significantly smaller than the wild-type, with the size difference evident from Day 7.5 and becoming more disparate as development progresses. These morphological data further support the genetic evidence indicating that the developmental lethality of the Rw mutation is not caused by the disruption of a gene within the cluster of RTKs in the central portion of mouse chromosome 5. Furthermore, we present evidence that both Kit and Pdgfra are expressed from the Rw chromosome in several adult tissues. The results of these studies suggest that the identification of the sequence(s) disrupted by the Rw mutation will provide further insight into the regulation of early postimplantation development.