EFFECTS OF H-2 HAPLOTYPES ON TROPHECTODERM DEVELOPMENT

对于t12突变纯合的小鼠胚胎死亡， 桑椹胚晚期，而那些纯合子的 t6突变在卵柱期早期或晚期死亡。 这些基因型的表型表现包括缺乏 滋养外胚层形成（t12/t12胚胎）及其随后的 分化（t6/t6胚胎）。 在后一种胚胎中， 滋养外胚层细胞不转化为巨细胞。 的确切 这些表型表达的原因尚不清楚。 也不是 已知缺陷是否由隐性致死T 单倍型或其连锁的独特H-2单倍型。 的手段 区分T单倍型的影响， 在早期胚胎发生中唯一的H-2单倍型是显微注射 野生型DNA的重叠序列覆盖T 单倍型区域或H-2单倍型区域转化为纯合的 突变合子，并确定哪些序列部分或 完全拯救了纯合T胚胎。 在拟议的系列中， 我们将在t12/t12和t6/t6受精卵中注射 野生型H-2 DNA的重叠序列，然后按照它们的 在体外和体内的后续发展。 积极成果 从这些研究将确定野生型H-2基因座的作用 在早期哺乳动物胚胎发育和 滋养外胚层及其衍生物。

Mouse embryos which are homozygous for the t12 mutation die at the late morula stage whereas those that are homozygous for the t6 mutation die at either the early or the late egg cylinder stage. The phenotypic expressions of these genotypes include the lack of trophectoderm formation (t12/t12 embryos) and its subsequent differentiation (t6/t6 embryos). In the latter embryos, the trophectoderm cells do not transform into giant cells. The exact cause(s) of these phenotypic expressions is not known. Nor is it known if the defects are caused by the recessive lethal T haplotypes or their linked, unique H-2 haplotypes. A means for distinguishing the effect of the T haplotype from that of the unique H-2 haplotype on early embryogenesis is to microinject overlapping sequences of wild-type DNA covering either the T haplotype region or the H-2 haplotype region into homozygous mutant zygotes and determine which sequence(s) partially or totally rescues the homozygous T embryos. In the proposed series of experiments we will inject t12/t12 and t6/t6 zygotes with overlapping sequences of wild-type H-2 DNA and then follow their subsequent development both in vitro and in vivo. Positive results from these studies will define the role of the wild-type H-2 locus in early mammalian embryogenesis and in the formation of the trophectoderm and its derivatives.