The preimplantation period of mammalian development is genetically controlled by both maternal and embryonic genes. One embryonic gene, Ped (Preimplantation embryo development), determines the rate (fast or slow) at which preimplantation mouse embryos cleave. In addition, the Ped gene has well-defined model system for the system for the study of early mammalian embryonic development and reproductive success. The molecular mechanisms by which the Ped gene product, a class I major histocompatibility complex (MHC) protein, the Qa-2 antigen, confers the Ped gene phenotype, will be evaluated. Only embryos expression Qa-2 antigen cleave at a fast rate. Four similar genes, Q6, Q7, Q8, and Q9 encode the Qa-2 antigen. The relative contribution of each of these genes to the various manifestations of Ped gene phenotype is unknown, but it has been shown, by the analysis of Q9 transgenic mice, that the Q9 gene controls the rate of cleavage division of early embryos. The contribution of the Q9 gene to the other aspects of Ped gene phenotype, litter size, birth weight, and weaning weight, will be analyzed. In addition, new lines of Q9 transgenic mice will be evaluated to determine whether chromosomal location or copy number of the Q9 gene affect Ped gene phenotype. Next, the type of membrane linkage of the Qa-2 antigen to the embryonic cell surface will be studied, by using Q9 exon-spliced gene constructs, to determine whether a glycosylphosphatidylinositol (GPI) linkage is required for Qa-2 antigen to signal embryos to cleave at a fast rate. The possible contribution to Ped gene phenotype of the other Qa-2 encoding genes, Q6, Q7, and Q8, will also be evaluated. Subtractive hybridization experiments will be used to classify any as yet unidentified genes that may contribute to the Ped gene phenotype. Also to be analyzed are the distribution of Qa-2 antigen on the embryonic cell surface and whether cross-linking of Qa-2 antigen on the embryonic cell surface and whether cross-linking of Qa-2 antigen on the embryonic cell surface can activate embryos to cleave at a faster rate. Finally, studies will be conducted to ascertain to their Qa-2 negative littermates, occurs. The finding that Ped gene product is a class I MHC protein is of fundamental interest because this suggests that the MHC class I family of proteins may be central importance to cell-cell interactions in development and reproduction as well as to cell-cell interactions in the immune response.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD031505-02
Application #
2204062
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Project Start
1994-05-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
2
Fiscal Year
1995
Total Cost
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
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
McElhinny, A S; Warner, C M (2000) Cross-linking of Qa-2 protein, the Ped gene product, increases the cleavage rate of C57BL/6 preimplantation mouse embryos. Mol Hum Reprod 6:517-22
McElhinny, A S; Exley, G E; Warner, C M (2000) Painting Qa-2 onto Ped slow preimplantation embryos increases the rate of cleavage. Am J Reprod Immunol 44:52-8
Ke, X; Warner, C M (2000) Regulation of Ped gene expression by TAP protein. J Reprod Immunol 46:15-Jan
Warner, C M; Paschetto, M G (2000) Analysis of mRNA levels for the MHC class I-like molecules CD1 and FcRn in preimplantation mouse embryos. Am J Reprod Immunol 43:234-9
Cao, W; Brenner, C A; Alikani, M et al. (1999) Search for a human homologue of the mouse Ped gene. Mol Hum Reprod 5:541-7
Exley, G E; Tang, C; McElhinny, A S et al. (1999) Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos. Biol Reprod 61:231-9
Wu, L; Feng, H; Warner, C M (1999) Identification of two major histocompatibility complex class Ib genes, Q7 and Q9, as the Ped gene in the mouse. Biol Reprod 60:1114-9
Exley, G E; Warner, C M (1999) Selection in favor of the Ped fast haplotype occurs between mid-gestation and birth. Immunogenetics 49:653-9
McElhinny, A S; Kadow, N; Warner, C M (1998) The expression pattern of the Qa-2 antigen in mouse preimplantation embryos and its correlation with the Ped gene phenotype. Mol Hum Reprod 4:966-71

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