(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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
1R01HD039215-01A1
Application #
6325493
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Taymans, Susan
Project Start
2001-04-15
Project End
2006-03-31
Budget Start
2001-04-15
Budget End
2002-03-31
Support Year
1
Fiscal Year
2001
Total Cost
$285,300
Indirect Cost
Name
Northeastern University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02115
Warner, Carol M; Lampton, Paula W; Newmark, Judith A et al. (2008) Symposium: innovative techniques in human embryo viability assessment. Soluble human leukocyte antigen-G and pregnancy success. Reprod Biomed Online 17:470-85
Byrne, Michael J; Warner, Carol M (2008) MicroRNA expression in preimplantation mouse embryos from Ped gene positive compared to Ped gene negative mice. J Assist Reprod Genet 25:205-14
Lampton, Paula W; Goldstein, Carmit Y; Warner, Carol M (2008) The role of tapasin in MHC class I protein trafficking in embryos and T cells. J Reprod Immunol 78:28-39
Lampton, P W; Crooker, R J; Newmark, J A et al. (2008) Expression of major histocompatibility complex class I proteins and their antigen processing chaperones in mouse embryonic stem cells from fertilized and parthenogenetic embryos. Tissue Antigens 72:448-57
Nagesha, D; Laevsky, G S; Lampton, P et al. (2007) In vitro imaging of embryonic stem cells using multiphoton luminescence of gold nanoparticles. Int J Nanomedicine 2:813-9
De Fazio, Sally R; Warner, Carol M (2007) Activation of T cells by cross-linking Qa-2, the ped gene product, requires Fyn. Am J Reprod Immunol 58:315-24
Newmark, Judith A; Warger 2nd, William C; Chang, ChihChing et al. (2007) Determination of the number of cells in preimplantation embryos by using noninvasive optical quadrature microscopy in conjunction with differential interference contrast microscopy. Microsc Microanal 13:118-27
Comiskey, Martina; Warner, Carol M (2007) Spatio-temporal localization of membrane lipid rafts in mouse oocytes and cleaving preimplantation embryos. Dev Biol 303:727-39
Comiskey, Martina; Domino, Kenneth E; Warner, Carol M (2007) HLA-G is found in lipid rafts and can act as a signaling molecule. Hum Immunol 68:1-11
Purnell, Elissa T; Warner, Carol M; Kort, Hilton I et al. (2006) Influence of the preimplantation embryo development (Ped) gene on embryonic platelet-activating factor (PAF) levels. J Assist Reprod Genet 23:269-73

Showing the most recent 10 out of 17 publications