Investigating the Biological Consequences of Aneuploidy in Early Embryogenesis

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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.