EFFECTS OF H-2 HAPLOTYPES ON TROPHECTODERM DEVELOPMENT

T12突变纯合的小鼠胚胎死于 桑拿期晚期，而那些纯合子的人 T6突变在卵筒的早期或晚期死亡。 这些基因型的表型表达包括缺乏 滋养外胚层的形成(T12/T12胚胎)及其后续 分化(T6/T6胚胎)。在后一种胚胎中， 滋养外胚层细胞不会转化为巨细胞。完全相同的 这些表型表达的原因(S)尚不清楚。也不是 已知缺陷是否由隐性致死性T细胞引起 单倍型或其链接的、唯一的H-2单倍型。一种手段 区分T单倍型和T单倍型的效应 早期胚胎发生的唯一H-2单倍型是微量注射 覆盖T细胞的野生型DNA的重叠序列 单倍型区域或H-2单倍型区域变为纯合子 突变受精卵并确定哪个序列(S)部分或 完全挽救了纯合子T胚胎。在建议的系列中 我们将给T12/T12和T6/T6受精卵注射 野生型H-2DNA的重叠序列，然后跟随它们的 随后在体外和体内都有发育。积极的结果 这些研究将确定野生型H-2基因座的作用 在哺乳动物早期胚胎发育和 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.