MOLECULAR BASIS OF THE PED GENE PHENOTYPE

点击翻译按钮获取中文摘要

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.