Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation
Gene therapy for progeny of mito-mice carrying pathogenic mtDNA by nuclear transplantation
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DOI：
10.1073/pnas.0506197102
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发表时间：
2005-11-15
影响因子：
11.1
通讯作者：
Hayashi, JI
中科院分区：
文献类型：
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作者：
Sato, A;Kono, T;Hayashi, JI
线粒体致病突变已被证明与呼吸缺陷的表达以及由此导致的线粒体疾病的表达有关。本研究利用线粒体受精卵的核移植技术，直接研究线粒体疾病的基因治疗问题。Mito小鼠表现出呼吸缺陷和线粒体疾病，这是由于携带大规模缺失的mtDNA(Delta MtDNA)积累所致。取第二极体作为活检标本，用于诊断有丝分裂小鼠受精卵的mtDNA基因分型。从有丝分裂小鼠的受精卵到去核的正常受精卵进行了核移植，结果表明，所有的F-0后代在一生中都没有表现出呼吸缺陷。这一方法应适用于线粒体疾病患者，以防止其子女发生这种疾病。
Pathogenic mutations in mtDNAs have been shown to be responsible for expression of respiration defects and resultant expression of mitochondrial diseases. This study directly addressed the issue of gene therapy of mitochondrial diseases by using nuclear transplantation of zygotes of transmitochondria mice (mito-mice). Mito-mice expressed respiration defects and mitochondrial diseases due to accumulation of mtDNA carrying a large-scale deletion (Delta mtDNA). Second polar bodies were used as biopsy samples for diagnosis of mtDNA genotypes of mito-mouse zygotes. Nuclear transplantation was carried out from mito-mouse zygotes to enucleated normal zygotes and was shown to rescue all of the F-0 progeny from expression of respiration defects throughout their lives. This procedure should be applicable to patients with mitochondrial diseases for preventing their children from developing the diseases.