MOLECULAR BASIS OF THE PED GENE PHENOTYPE

哺乳动物胚胎植入前的发育阶段， 由母体和胚胎基因共同控制。 一个胚胎基因， （植入前胚胎发育），决定速度（快或慢） 植入前小鼠胚胎分裂的时间。 此外，Ped基因 具有明确的模型体系，可供系统早期研究 哺乳动物胚胎发育和生殖成功。 分子 Ped基因产物，一种I类主要的 组织相容性复合体（MHC）蛋白，Qa-2抗原，赋予免疫原性。 将评价Ped基因表型。 只有胚胎表达Qa-2 抗原以较快速度裂解。 四个相似的基因，Q6，Q7，Q8和Q9 编码Qa-2抗原。 每一个的相对贡献 基因对Ped基因表型的各种表现尚不清楚，但 通过对Q9转基因小鼠的分析表明，Q9 基因控制着早期胚胎的卵裂率。 的 Q9基因对Ped基因表型的其他方面的贡献， 分析窝仔数、出生体重和断奶体重。 在 此外，将评估Q9转基因小鼠的新品系，以确定 Q9基因的染色体位置或拷贝数是否影响Ped 基因表型 接下来，Qa-2抗原的膜连接类型 胚胎细胞表面将被研究，通过使用Q9外显子拼接 基因构建，以确定糖基磷脂酰肌醇 (GPI)Qa-2抗原需要连接以向胚胎发出切割信号 以很快的速度。 Ped基因表型的可能贡献 也将评估其它Qa-2编码基因Q6、Q7和Q8。 差减杂交实验将用于分类任何尚未 未鉴定的基因可能有助于Ped基因表型。 也 待分析的是Qa-2抗原在胚胎细胞上的分布 Qa-2抗原在胚胎细胞表面是否交联 Qa-2抗原在胚胎细胞表面是否交联 表面可以激活胚胎以更快的速度分裂。 最后， 将进行研究，以确定他们的Qa-2阴性 littermates，发生。 发现Ped基因产物是I类MHC 蛋白质是根本的兴趣，因为这表明， I类蛋白质家族可能是细胞-细胞 在发育和生殖以及细胞间的相互作用 免疫反应中的相互作用。

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.