Recessive Mutations that Disrupt Develop of Mouse Embryo

描述（由申请人提供）：基因组技术的最新进展使得应用基于表型的筛选来鉴定在哺乳动物发育过程中发挥重要作用的基因成为可能。在斯隆-凯特林研究所已经进行的ENU突变筛选中，已经确定了41种破坏胚胎发生特定方面的隐性致死突变。在基因组特定区域的30个突变中，发现三个是先前定义的基因的等位基因。大多数新突变影响的是以前不知道在哺乳动物发育中起作用的基因。现有的41个突变将被描述为提供足够的信息，其他对发育的特定方面感兴趣的研究人员将能够识别这些突变，从而推进他们的研究。每个突变将获得三种信息：发育停止时的形态；地图位置;以及信息分子标记的表达。将建立一个网站，向社区提供有关这些突变的信息，并向感兴趣的研究人员提供来自突变系的冷冻精子。

DESCRIPTION (provided by applicant): Recent advances in genome technology have made it possible to apply phenotype-based screens to identify genes that perform roles of fundamental importance during mammalian development. In ENU mutagenesis screens already carried out at Sloan-Kettering Institute, 41 recessive lethal mutations that disrupt specific aspects of embryogenesis have been identified. Of 30 mutations mapped to specific regions of the genome, three were found to be alleles of previously defined genes. Most of the new mutations affect genes that were not previously known to play a role in mammalian development. The 41 existing mutations will be characterized to provide enough information that other investigators interested in specific aspects of development will be able to identify those mutations that will advance their research. Three kinds of information will be obtained for each mutation: the morphology at the time of developmental arrest; map position; and expression of informative molecular markers. A website will be developed to make the information about these mutations available to the community and frozen sperm from mutant lines will be made available to interested investigators. Five investigators will combine their expertise to perform new screens to identify recessive mutations that cause defects in specific developmental processes at three stages of gestation, e9.5, e12.5, and e18.5. The e9.5 screen will identify mutants based on abnormal external morphology and abnormalities in gene silencing (genomic imprinting, retroposon silencing, and Xist expression in males). The e12.5 screen will identify mutants based on abnormal external morphology and inappropriate expression of molecular markers of neural patterning. The e18.5 screen will identify mutants based on abnormal external morphology, abnormal morphology of the genitourinary tract, and abnormal histology of the kidney. Information about the new mutants will be entered on website, and frozen sperm made available to interested investigators. For a small number of genes of interest to the consortium, map-based approaches will be used to identify the genes responsible for the mutant phenotype. All new polymorphic mapping markers and new methods will be made available to the community as electronic resources.