Investigating the Biological Consequences of Aneuploidy in Early Embryogenesis

描述（由申请人提供）：本项目汇集了杰克逊实验室（TJL;持有P40 RR 001183，小鼠突变资源的机构）和密歇根大学临床健康与研究学院，密歇根大学（U-M）的临床和转化科学获奖者。参与该项目的具体小组是TJL的遗传资源科学小组，密歇根大学转基因动物模型核心设施（ABMR大学）和U-M妇产科系（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，以检查非整倍性，即染色体数目异常的情况，如何影响早期胚胎发育，使用几种迄今为止尚未获得的遗传小鼠模型。非整倍体是产前丢失的最常见遗传原因，也是产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还知之甚少，而且目前鉴定人类胚胎非整倍体的方法也不可靠。将使用最先进的技术在发育、基因表达和代谢方面评估非整倍体和整倍体胚胎，这些数据将用于开发选择通过辅助生殖技术产生的整倍体胚胎的新方法。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深入了解，并且还将提供关于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。这些资源将是宝贵的非整倍体的研究。这个项目与P40奖的资助非常吻合，P40奖为人类疾病建立了小鼠模型。此外，它有望建立一个框架，并为临床相关的研究计划产生重要的初步数据。 公共卫生相关性（由申请方提供）：这些染色体异常小鼠胚胎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验证染色体异常的胚胎。这些研究可能有助于降低染色体异常儿童的出生率，也可能提高体外受精的成功率。

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.