GENETIC ANALYSIS OF MAMMALIAN MITOCHONDRIAL INHERITANCE

哺乳动物线粒体遗传的基因分析

• 批准号: 3283405
• 负责人: PHILIP J LAIPIS
• 金额: $ 12.65万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1988-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3283405
• 关键词: animal population genetics; biological polymorphism; cytogenetics; genetic manipulation; genotype; mitochondrial DNA; tissue /cell culture

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.

我们建议构建两种不同的异质性小鼠， 通过显微注射遗传标记的线粒体DNA 受精卵，然后将这些卵重新植入 合适的母亲。 然后我们将遵循随后的分离， 这些线粒体既存在于异质动物自身的组织中， 任何雌性动物的正常后代。 结果将用于 测试我们提出的线粒体分离模型。 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， 线粒体群体在母体中传递给后代， 线粒体的遗传 如果成功，这些研究将扩大 研究发育途径，跨物种杂交， 提出了胚胎药物筛选的可能性。 此外，如果显微注射到小鼠卵母细胞是成功的，我们将 根据我们对牛卵母细胞和偶蹄动物线粒体的经验， 通过将这些基因操作扩展到奶牛中来实现基因型。 我们 不仅会构建种内杂种（即，奶牛品种之间 具有不同的mtDNA限制性图谱），但也可以构建杂交 在相关的牛科物种之间，测量进化距离， 发育相容性 这里开发的方法将奠定一个 未来体外基因操作的基础 线粒体基因组