BIOCHEMISTRY OF EARLY MAMMALIAN DEVELOPMENT

两种影响哺乳动物胚胎发育的遗传异常将在 研究了 寡并指（Os）和显性黄色（Ay）都是 以杂合形式引起发育异常的突变 在纯合子形式下导致早期胚胎死亡。 自从Ay 突变似乎与亲嗜性病毒的插入有关， 将使用探针研究这种突变的分子基础， 针对Ay相关的前病毒整合位点和侧翼 宿主DNA序列 agglutinin基因座的正常mRNA转录本将 在早期胚胎中识别并评估突变的影响。 将制备Ay/Ay畸胎瘤细胞系，且Ay/Ay等于+/+ 分析嵌合体。 研究纠正Ay/Ay细胞中的缺陷， 在+/+细胞中复制缺陷将通过显微注射 克隆DNA 双丁酰cAMP对Ay/Ay胚胎发育能力的影响 将评估体外孵化。 的关系 的杂合子表现和有丝分裂缺陷的鉴定， 将分析Os/Os胚胎。 Os/+卵细胞增殖 圆柱体和肢芽将被确定，和钙的效果 离子电话，A23187，评估。

Two genetic abnormalities affecting mammalian embryonic development will be investigated. Oligosyndactyly (Os) and dominant yellow (Ay) are both mutations which in the heterozygous form cause developmental abnormalities and in the homozygous form cause early embryonic death. Since the Ay mutation appears to be associated with the insertion of an ecotropic virus, the molecular basis of this mutation will be studied using probes to be developed against the Ay-associated proviral integration site and flanking host DNA sequences. The normal mRNA transcripts of the agouti locus will be identified in early embryos and the effects of the mutation assessed. Ay/Ay teratocarcinoma cell lines will be prepared and Ay/Ay equal to +/+ chimeras analyzed. Studies to correct the defect in Ay/Ay cells and to reproduce the defect in +/+ cells will be undertaken by microinjection of cloned DNA. The effect of dibutyryl cAMP on the ability of Ay/Ay embryos to hatch in vitro will be assessed. The relationship between the heterozygous manifestations of Os and the mitotic defect identified in Os/Os embryos will be analyzed. Cellular proliferation in Os/+ egg cylinders and limb buds will be determined, and the effect of the calcium ionophone, A23187, assessed.