Investigating the Biological Consequences of Aneuploidy in Early Embryogenesis

研究早期胚胎发生中非整倍性的生物学后果

• 批准号: 7744096
• 负责人: MURIEL T DAVISSON
• 金额: $ 46.12万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744096
• 关键词: Address; Affect; Aneuploidy; Animal Model; Arts; Assisted Reproductive Technology; Award; Biological; Biological Markers; Biopsy; Birth; Cell Line; Cell physiology; Cells; Child; Chromosome abnormality; Chromosomes; Clinical; Communities; Core Facility; Data; Development; Discipline of obstetrics; Disease; Down Syndrome; ES Cell Line; Embryo; Embryo Research; Embryonic Development; Energy Metabolism; Evaluation; Female; Fertilization in Vitro; Frequencies; Gene Expression; Genetic; Genetic Models; Germ Cells; Goals; Gynecology; Haploidy; Health; Homozygote; Human; Incidence; Institutes; Institution; Laboratories; Laboratory Research; Metabolism; Methods; Michigan; Modeling; Monosomy; Morbidity - disease rate; Morphology; Mus; Mutant Strains Mice; Ovary; Parents; Predictive Value; Pregnancy loss; Production; Recovery; Research; Resources; Science; Study models; Technology; Transgenic Animals; Trisomy; Trisomy 4; Universities; autosome; base; clinically relevant; embryonic stem cell; genetic analysis; improved; insight; male; metabolomics; mortality; mouse model; novel strategies; postnatal; prenatal; programs; public health relevance; sperm cell; success; transcriptomics

DESCRIPTION (provided by applicant): This project brings together The Jackson Laboratory (TJL; the Institution holding P40RR001183, Mouse Mutant Resource), and the Michigan Insfitute of Clinical Health and Research, a Clinical and Translafional Science Awardee at the University of Michigan (U-M). The specific groups participating in this project are the Genefic Resources Sciences group at TJL, the University of Michigan Transgenic Animal Model Core Facility (a university ABMR) and a research laboratory in the U-M Department of Obstetrics and Gynecology (CTSA affiliates). The goals of this proposal are to develop resources and initiate studies to examine how aneuploidy, conditions in which there are abnormal numbers of chromosomes, affects early embryonic development using several hitherto unavailable genetic mouse models. Aneuploidy is the most common genefic cause of prenatal loss and also is a significant cause of postnatal morbidity and mortality. At present, little is understood about how aneuploidy affects eariy embryonic development, and current methods to identify aneuploidy in human embryos are unreliable. Aneuploid and euploid embryos will be evaluated In terms of development, gene expression and metabolism using state-of-the-art technologies and these data will be used to develop new approaches for selection of euploid embryos created by assisted reproductive technologies. Data from these studies will provide insight into how aneuploidy affects eariy development and will also provide important phenotypic information about several genetic models. This project will also generate cryopreserved gamete and ES cell resources that will be available to the research community. These resources will be valuable for a number of studies of aneuploidy. This project fits well with the alms of the parent P40 award, which generates mouse models for human disorders. Furthermore, it promises to build a framework and generate important preliminary data for a clinically relevant research program. Public Health Relevance (provided by applicant): The goal of these studies of mouse embryos with chromosomal abnormalities is to better understand how chromosomal abnormalities affect eariy prenatal development and develop better methods to idenfify embryos that are chromosomally abnormal. These studies may help to reduce the incidence of the birth of children with chromosomal abnormalifies and may also improve the success of in vitro fertilization.

描述（由申请人提供）：该项目汇集了杰克逊实验室（TJL；持有 P40RR001183、小鼠突变资源的机构）和密歇根临床健康与研究研究所（密歇根大学临床和转化科学奖获得者） ）。参与该项目的具体小组包括 TJL 的基因资源科学小组、密歇根大学转基因动物模型核心设施（大学 ABMR）和密歇根大学妇产科（CTSA 附属机构）的研究实验室。该提案的目标是开发资源并启动研究，以使用几种迄今为止无法获得的遗传小鼠模型来检查非整倍性（染色体数量异常的情况）如何影响早期胚胎发育。非整倍体是产前丢失的最常见遗传原因，也是产后发病和死亡的重要原因。目前，人们对非整倍性如何影响早期胚胎发育知之甚少，并且目前识别人类胚胎中非整倍性的方法并不可靠。将使用最先进的技术对非整倍体和整倍体胚胎的发育、基因表达和代谢进行评估，这些数据将用于开发选择辅助生殖技术产生的整倍体胚胎的新方法。这些研究的数据将深入了解非整倍性如何影响早期发育，还将提供有关几种遗传模型的重要表型信息。该项目还将产生冷冻保存的配子和 ES 细胞资源，供研究界使用。这些资源对于非整倍体的许多研究都很有价值。该项目与母公司 P40 奖项的捐赠非常契合，该奖项旨在生成人类疾病的小鼠模型。此外，它还承诺为临床相关研究项目建立一个框架并生成重要的初步数据。 公共健康相关性（由申请人提供）：这些对染色体异常小鼠胚胎的研究的目的是更好地了解染色体异常如何影响早期产前发育，并开发更好的方法来识别染色体异常的胚胎。这些研究可能有助于减少染色体异常儿童的出生率，也可能提高体外受精的成功率。