Meirelles F V, Smith L C
Centre de recherche en reproduction animale, Faculté de médecine vétérinaire, Université de Montréal, Saint-Hyacinthe, Québec, Canada.
Genetics. 1997 Feb;145(2):445-51. doi: 10.1093/genetics/145.2.445.
Mitochondrial genotypes have been shown to segregate both rapidly and slowly when transmitted to consecutive generations in mammals. Our objective was to develop an animal model to analyze the patterns of mammalian mitochondrial DNA (mtDNA) segregation and transmission in an intraspecific heteroplasmic maternal lineage to investigate the mechanisms controlling these phenomena. Heteroplasmic progeny were obtained from reconstructed blastocysts derived by transplantation of pronuclearstage karyoplasts to enucleated zygotes with different mtDNA. Although the reconstructed zygotes contained on average 19% mtDNA of karyoplast origin, most progeny contained fewer mtDNA of karyoplast origin and produced exclusively homoplasmic first generation progeny. However, one founder heteroplasmic adult female had elevated tissue heteroplasmy levels, varying from 6% (lung) to 69% (heart), indicating that stringent replicative segregation had occurred during mitotic divisions. First generation progeny from the above female were all heteroplasmic, indicating that, despite a meiotic segregation, they were derived from heteroplasmic founder oocytes. Some second and third generation progeny contained exclusively New Zealand Black/BINJ mtDNA, suggesting but not confirming, an origin from an homoplasmic oocyte. Moreover, several third to fifth generation individuals maintained mtDNA from both mouse strains, indicating a slow or persistent segregation pattern characterized by diminished tissue and litter variability beyond second generation progeny. Therefore, although some initial lineages appear to segregate rapidly to homoplasmy, within two generations other lineages transmit stable amounts of both mtDNA molecules, supporting a mechanism where mitochondria of different origin may fuse, leading to persistent intraorganellar heteroplasmy.
线粒体基因型在哺乳动物中传递给连续几代时，已显示出快速和缓慢的分离现象。我们的目标是建立一种动物模型，以分析种内异质性母系谱系中哺乳动物线粒体DNA（mtDNA）的分离和传递模式，从而研究控制这些现象的机制。通过将原核期核质体移植到具有不同mtDNA的去核受精卵中获得重构囊胚，进而得到异质性后代。尽管重构受精卵平均含有19%核质体来源的mtDNA，但大多数后代含有较少的核质体来源的mtDNA，并且只产生纯质性的第一代后代。然而，有一只异质性成年雌性奠基者的组织异质性水平有所升高，从6%（肺）到69%（心脏）不等，这表明在有丝分裂过程中发生了严格的复制分离。上述雌性的第一代后代均为异质性，这表明尽管经过了减数分裂分离，但它们来源于异质性的奠基者卵母细胞。一些第二代和第三代后代只含有新西兰黑/宾州日本小鼠（New Zealand Black/BINJ）的mtDNA，这暗示但未证实其来源于纯质性卵母细胞。此外，一些第三代至第五代个体同时保留了两个小鼠品系的mtDNA，这表明存在一种缓慢或持续的分离模式，其特征是第二代后代之后组织和窝内的变异性减小。因此，尽管一些初始谱系似乎迅速分离为纯质性，但在两代之内，其他谱系会稳定传递两种mtDNA分子，这支持了一种机制，即不同来源的线粒体可能融合，导致细胞器内持续存在异质性。
