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的机构，小鼠突变资源)和密歇根大学临床健康与研究研究所，密歇根大学临床和跨性别科学奖(密歇根大学)。参与该项目的具体小组是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(一所大学ABMR)和密歇根大学妇产科的一个研究实验室(CTSA附属机构)。这项提议的目标是开发资源并启动研究，以利用几个迄今无法获得的遗传小鼠模型来检查非整倍体如何影响早期胚胎发育。非整倍体是导致产前损失的最常见的基因原因，也是导致出生后发病率和死亡率的重要原因。目前，人们对非整倍体如何影响早期胚胎发育知之甚少，目前鉴定人类胚胎中非整倍体的方法也是不可靠的。将使用最先进的技术从发育、基因表达和新陈代谢方面对非整倍体和整倍体胚胎进行评估，这些数据将被用于开发通过辅助生殖技术创造的整倍体胚胎选择的新方法。来自这些研究的数据将提供对非整倍体如何影响早期发育的洞察，也将提供关于几种遗传模式的重要表型信息。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。这些资源将对一些非整倍体的研究有价值。这个项目非常符合父母P40奖的施舍，该奖项为人类疾病创造了小鼠模型。此外，它承诺为临床相关的研究计划建立一个框架并产生重要的初步数据。 公共卫生相关性(由申请者提供)：这些对染色体异常小鼠胚胎的研究的目标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降低染色体异常儿童的出生发生率，也可能提高体外受精的成功率。