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）：该项目将杰克逊实验室（TJL；持有P40RR001183的机构持有）和密歇根大学（U-M）的临床和翻译科学奖（U-M）的临床和翻译科学奖。参加该项目的特定小组是TJL的Genefic Resources Sciences小组，密歇根大学转基因动物模型核心设施（A ABMR）和U-M妇产科科学系（CTSA关联公司）的研究实验室。该提案的目标是开发资源并开始研究，以研究异倍型，染色体数量异常的条件如何使用迄今无法使用的几种无法获得的遗传小鼠模型来影响早期胚胎发育。非整倍性是产前丧失的最常见基因性原因，也是产后发病率和死亡率的重要原因。目前，关于非整倍性如何影响胚胎发育的目前，鉴定人类胚胎中的非整倍性的方法几乎没有理解。使用最先进的技术，将根据发育，基因表达和代谢来评估非整倍体和整倍体胚胎，这些数据将用于开发新的方法，以选择由辅助生殖技术创建的息肉胚胎。这些研究的数据将提供有关针对性如何影响耳朵发育的洞察力，还将提供有关几种遗传模型的重要表型信息。该项目还将生成冷冻保存配子和ES细胞资源，并将为研究社区提供。这些资源对于许多非整倍性研究将很有价值。该项目非常符合父级P40奖的施舍，该奖项生成了人类疾病的鼠标模型。此外，它有望建立一个框架并为临床相关研究计划生成重要的初步数据。 公共卫生相关性（由申请人提供）：这些对具有染色体异常的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耳朵产前发育，并开发出更好的方法来iDenfife染色体异常的胚胎。这些研究可能有助于减少染色体异常的儿童出生的发生率，并可能改善体外受精的成功。