Accumulation of pathogenic ΔmtDNA induced deafness but not diabetic phenotypes in mito-mice
Accumulation of pathogenic ΔmtDNA induced deafness but not diabetic phenotypes in mito-mice
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DOI：
10.1016/j.bbrc.2004.08.073
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发表时间：
2004-10-08
影响因子：
3.1
通讯作者：
Hayashi, J
中科院分区：
文献类型：
--
作者：
Nakada, K;Sato, A;Hayashi, J
通过将来自培养细胞的DeltamtDNA导入C57 BL/6.1（136）品系小鼠的受精卵中，产生了携带不同比例的缺失突变mtDNA（DeltamtDNA）的线粒体小鼠。有丝分裂小鼠的巨大优势在于它们具有完全相同的核基因组背景，并且它们的遗传变异仅限于致病性DeltamtDNA的比例。由于DeltamtDNA积累到超过75%诱导呼吸缺陷，在携带超过75%DeltamtDNA的线粒体小鼠中观察到的疾病表型应该是由于积累的DeltamtDNA。在这项研究中，我们专注于听力损失和糖尿病表型的表达，因为这些常见的年龄相关的异常有时被报道为母系遗传，并与致病突变的mtDNA。结果表明，外源性导入DeltamtDNA的积累是导致听力损失的原因，但不是导致糖尿病表型在线粒体小鼠中的表达。(C)2004年爱思唯尔公司All rights reserved.
Mito-mice carrying various proportions of deletion mutant mtDNA (DeltamtDNA) were generated by introduction of the DeltamtDNA from cultured cells into fertilized eggs of C57BL/6.1 (136) strain mice. Great advantages of mito-mice are that they share exactly the same nuclear-genome background, and that their genetic variations are restricted to proportions of pathogenic DeltamtDNA. Since accumulation of DeltamtDNA to more than 75% induced respiration defects, the disease phenotypes observed exclusively in mito-mice carrying more than 75% DeltamtDNA should be due to accumulated DeltamtDNA. In this study, we focused on the expressions of hearing loss and diabetic phenotypes, since these common age-associated abnormalities have sometimes been reported to be inherited maternally and to be associated with pathogenic mutant mtDNAs. The results showed that accumulation of exogenously introduced DeltamtDNA was responsible for hearing loss, but not for expression of diabetic phenotypes in mito-mice. (C) 2004 Elsevier Inc. All rights reserved.