Recessive Mutations that Disrupt Develop of Mouse Embryo

破坏小鼠胚胎发育的隐性突变

• 批准号: 6666630
• 负责人: Kathryn V Anderson
• 金额: $ 95.64万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-25 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6666630
• 关键词: animal breeding; autosomal recessive trait; biomarker; biotechnology; cooperative study; cryopreservation; developmental genetics; embryogenesis; ethanol; gene mutation; genetic mapping; genetic screening; information dissemination; laboratory mouse; lethal genes; morphometry

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.

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识别在哺乳动物发育过程中发挥基本重要性作用的基因。 在Sloan-Kettering Institute已经进行的ENU诱变筛查中，已经确定了破坏胚胎发生特定方面的41个隐性致命突变。 在映射到基因组特定区域的30个突变中，发现三个是先前定义的基因的等位基因。 大多数新突变会影响以前未知在哺乳动物发育中发挥作用的基因。 现有的41个突变将被表征，以提供足够的信息，其他对开发特定方面感兴趣的研究人员将能够识别那些将推进其研究的突变。 每个突变将获得三种信息：发育停滞时的形态；地图位置；和信息性分子标记的表达。 将开发一个网站，以使社区可用的这些突变的信息，并将从突变系列中冻结的精子提供给感兴趣的研究人员。 五名研究人员将结合他们的专业知识来执行新的筛选，以识别妊娠三个阶段E9.5，E12.5和E18.5在特定发育过程中导致缺陷的隐性突变。 E9.5屏幕将基于基因沉默异常的外部形态和异常（基因组印记，逆膜沉默和男性中的Xist表达）鉴定突变体。 E12.5屏幕将基于神经模式的分子标记的异常外形态和不适当表达鉴定突变体。 E18.5屏幕将基于基于异常的外部形态，泌尿生殖道异常形态和肾脏异常组织学鉴定突变体。 有关新突变体的信息将在网站上输入，并提供给感兴趣的研究人员的冷冻精子。 对于财团感兴趣的少数基因，将使用基于地图的方法来识别负责突变表型的基因。 所有新的多态性映射标记和新方法将作为电子资源提供给社区。