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利用DNA交换避免线粒体遗传疾病的信息分析
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下一篇 2009-08-28 10:08:58
据《
自然》网站报道,线粒体DNA只会由母亲传给后代,因为精子中的线粒体并不向胚胎贡
献DNA。线粒体DNA突变与许多
疾病存在关联,比如Ⅱ型糖尿病、线粒体肌病以及Leigh综合症(常见于婴儿的神经退化性疾病)等。如今,一种在卵
细胞
间转移
遗传物质的新
技术有望被用来预防由线粒体DNA突变导致的遗传性疾病。
美国俄勒冈州国家灵长类动物研究中心的Shoukhrat Mitalipov及其小组以恒河猴为实验对象,将一个卵细胞中的核DNA移入另一个去核卵细胞中,之后进行授精并植入子宫。这样生下的后代将具有一个母体的线粒体DNA和另一个母体的核DNA。
共15个胚胎被植入9个代孕母体,3个成功怀孕,其中1个为双胞胎,共产下4个后代。这与人类中的试管授精成功率相当。相关论文报告8月26日在线发表于《自然》杂志。该论文共报告了其中的3个后代,目前没有发现异常状况。
线粒体疾病研究界对此研究感到鼓舞。澳大利亚墨尔本默多克儿童研究所专攻线粒体疾病的遗
传学家David
Thorburn表示,该研究屏除了所有携带致病突变的线粒体DNA,而且是在灵长类动物中完成的,这使得该研究“具有高度的创新意义,非常有前途”,“
它应该能够比小鼠更近地模拟人类状况,如果能在人体中证明
安全,将是一个巨大的进步”。美国联合线粒体疾病基金会
科学与医学顾问委员会成员、迈阿密大学细
胞
生物学家Carlos Moraes说:“(这类)研究需要成本,也存在风险,但获益大于弊端。”
Nature advance online publication 26 August 2009 | :10.1038/nature08368:10.1038/nature08368; Received 29 June 2009; Accepted 10 August 2009; Published online 26 August 2009
Mitochondrial gene replacement in primate offspring and embryonic stem cells
Masahito Tachibana1, Michelle Sparman1, Hathaitip Sritanaudomchai1, Hong Ma1, Lisa Clepper1, Joy Woodward1, Ying Li1, Cathy Ramsey1, Olena Kolotushkina1 & Shoukhrat Mitalipov1,2,3
- Oregon National Primate Research Center,
- Oregon Stem Cell Center and,
- Departments of Obstetrics and Gynecology and Molecular and Medical Genetics, Oregon Health and Science University, 505 N.W. 185th Avenue, Beaverton, Oregon 97006, USA
Correspondence to: Shoukhrat Mitalipov1,2,3 Correspondence and requests for materials should be addressed to S.M. (Email: mitalipo@ohsu.edu).
Top of page
Abstract
Mitochondria are found in all eukaryotic cells and
contain their own genome (mitochondrial DNA or mtDNA). Unlike the
nuclear genome, which is derived from both the egg and sperm at
fertilization, the mtDNA in the embryo is derived almost exclusively
from the egg; that is, it is of maternal origin. Mutations in mtDNA
contribute to a diverse range of currently incurable human diseases and
disorders. To establish preclinical models for new therapeutic
approaches, we demonstrate here that the mitochondrial genome can be
efficiently replaced in mature non-human primate oocytes (Macaca mulatta)
by spindle–chromosomal complex transfer from one egg to an enucleated,
mitochondrial-replete egg. The reconstructed oocytes with the
mitochondrial replacement were capable of supporting normal
fertilization, embryo development and produced healthy offspring.
Genetic analysis confirmed that nuclear DNA in the three infants born
so far originated from the spindle donors whereas mtDNA came from the
cytoplast donors. No contribution of spindle donor mtDNA was detected
in offspring. Spindle replacement is shown here as an efficient
protocol replacing the full complement of mitochondria in newly
generated embryonic stem cell lines. This approach may offer a
reproductive option to prevent mtDNA disease transmission in affected
families.
信息分析平台:http://www.gopubmed.org/web/gopubmed/
检索策略:lMitochondrial DNA mutation and primate and mtDNA disease transmission
分析结果:
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