PED GENE ACTION IN DEVELOPMENT AND REPRODUCTION

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DESCRIPTION: (Scanned from the applicant's description): The survival of preimplantation mammalian embryos, and the health of offspring arising from these embryos, is regulated by genes expressed during the preimplantation period of development. One example is the mouse Preimplantation embryo development (Ped) gene. The Ped gene has pleiotropic effects on the rate of embryonic cleavage division, survival to term, birth weight, and weaning weight. The Ped gene product has been identified as the major histocompatibility complex (MHC) encoded class lb protein Qa-2. Mouse embryos that express Qa-2 protein cleave at a faster rate, have a higher chance of survival to birth, and give rise to pups with higher birth and weaning weights than embryos that do not express Qa-2. The mystery is how the presence of a protein on the embryonic cell surface can signal the embryo to cleave at a faster rate than an embryo that is missing this protein. The finding that the Ped gene product is a MHC class Ib protein provides clues about what structural features to examine to solve this mystery. First, the nonameric peptides that bind to Qa-2 protein will be identified by using the technique of membrane preconcentration-capillary electrophoresis-tandem mass spectrometry (mPC-CE-MSfMS). Second, the types of accessory proteins that bind to Qa-2 protein to help mediate its function will be identified by using the yeast two-hybrid system. The important pleiotropic effects of the Ped gene on reproductive success make it desirable to search for a human homolog of this gene. The publication of the complete DNA sequence of the human MHC (HLA complex), along with recent literature on MHC class lb proteins encoded in the HLA complex, suggest that the most logical hypothesis is that a human homolog of Qa-2 is HLA-G. This hypothesis will be tested in the third specific aim by using an HLA-G transgenic mouse system.