Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion

Application of ES cells for generation of respiration-deficient mice carrying mtDNA with a large-scale deletion
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DOI:
10.1016/j.bbrc.2005.05.155
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发表时间:
2005-07-29
影响因子:
3.1
通讯作者:
Hayashi, JI
Hayashi, JI
中科院分区:
生物学4区
文献类型:
--
作者:
Ishikawa, K;Kasahara, A;Hayashi, JI

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在之前的研究中,我们使用小鼠受精卵作为具有大规模缺失突变(Delta MtDNA)的mtDNA的受体,并产生携带Delta mtDNA的呼吸缺陷小鼠(mito小鼠)。在本研究中,我们使用小鼠ES细胞作为Delta mtDNA的受体,只有当ES细胞携带17%Delta mtDNA时,才能产生Delta mtDNA的有丝分裂小鼠。从携带超过61%Delta mtDNA的ES细胞中未获得嵌合体小鼠或其F_1后代。这些观察表明,ES细胞的呼吸缺陷抑制了它们向嵌合体小鼠和有丝分裂小鼠的正常分化,并且ES细胞比受精卵更有效地产生携带mtDNA而没有显著致病突变的有丝分裂小鼠。(C)2005 Elsevier Inc.保留所有权利。
In a previous study, we used mouse zygotes as recipients of mtDNA with a large-scale deletion mutation (Delta mtDNA) and generated respiration-deficient mice (mito-mice) carrying Delta mtDNA. In this study, we used mouse ES cells as recipients of Delta mtDNA, and generated mito-mice with Delta mtDNA only when the ES cells carried 17% Delta mtDNA. No chimera mice or their F, progenies were obtained from ES cells carrying more than 61% Delta mtDNA. These observations suggest that respiratory defects of ES cells inhibit their normal differentiation into chimera mice and mito-mice, and that ES cells are more effective than zygotes for generation of mito-mice carrying mtDNAs without significant pathogenic mutations. (c) 2005 Elsevier Inc. All rights reserved.