GENETIC ANALYSIS OF MAMMALIAN MITOCHONDRIAL INHERITANCE

我们建议构建两种不同的异质性小鼠 显微注射基因标记的线粒体DNA 变成受精卵，然后把这些卵子重新移植到 合适的寄宿母亲。然后我们将遵循随后的隔离 这些线粒体既存在于异质动物自身的组织中，也存在于组织中 在任何雌性动物的正常后代中。结果将被用来 对我们提出的线粒体分离模型进行检验。这些 模型表明线粒体DNA扩增和/或分离 在卵母细胞发育过程中导致选择次要成分 母体发育过程中传给子代的线粒体群体 线粒体的遗传。如果成功，这些研究将得到扩大 研究发育途径，跨物种杂交，以及 并提出了胚胎药物选择的可能性。 此外，如果显微注射小鼠卵母细胞成功，我们将 唤起我们对牛卵母细胞和偶趾龙线粒体的经验 通过将这些基因操作推广到奶牛身上来进行基因分型。我们 将不仅构建种内杂交(即，奶牛品种之间的杂交 具有不同的mtDNA限制模式)，但也构建了杂交 在近缘牛种之间，测量进化距离和 发育相容。这里开发的方法将为 为未来体外基因操作奠定基础 线粒体基因组。

We propose to construct mice which are heteroplasmic for two different mitochondrial DNAs by microinjection of genetically marked mitochondria into fertilized eggs and subsequent reimplantation of those eggs into a suitable host mother. We will then follow the subsequent segregation of these mitochondria both in tissues of the heteroplasmic animal itself and in the normal offspring of any female animals. The results will be used to test the models of mitochondrial segregation we have proposed. These models suggest that mitochondrial DNA amplification and/or segregation during oocyte development result in the selection of minor components of the mitochondrial population which are passed on to progeny during maternal inheritance of mitochondria. If successful, these studies will be expanded to examine developmental pathways, cross-species hybridization, and the possibility of embryonic drug selection are also proposed. Additionally, if microinjection into murine oocytes is successful, we will call upon our experience with bovine oocytes and artiodactyl mitochondrial genotypes by extending these genetic manipulations into dairy cows. We will construct not only intra-specific hybrids (i.e., between cow breeds with distinct mtDNA restriction patterns), but also construct crosses between related bovid species, to measure both evolutionary distance and developmental compatibility. The methods developed here would lay a foundation for the future in vitro genetic manipulation of the mitochondrial genome.