MRL小鼠中自然存在的线粒体DNA异质性
Naturally occurring mitochondrial DNA heteroplasmy in the MRL mouse.
作者信息
Sachadyn Paweł, Zhang Xiang-Ming, Clark Lise Desquenne, Naviaux Robert K, Heber-Katz Ellen
机构信息
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
出版信息
Mitochondrion. 2008 Dec;8(5-6):358-66. doi: 10.1016/j.mito.2008.07.007. Epub 2008 Aug 12.
The MRL/MpJ mouse is an inbred laboratory strain of Mus musculus, known to exhibit enhanced autoimmunity, increased wound healing, and increased regeneration properties. We report the full-length mitochondrial DNA (mtDNA) sequence of the MRL mouse (Accession # EU450583), and characterize the discovery of two naturally occurring heteroplasmic sites. The first is a T3900C substitution in the TPsiC loop of the tRNA methionine gene (tRNA-Met; mt-Tm). The second is a heteroplasmic insertion of 1-6 adenine nucleotides in the A-tract of the tRNA arginine gene (tRNA-Arg; mt-Tr) at positions 9821-9826. The level of heteroplasmy varied independently at these two sites in MRL individuals. The length of the tRNA-Arg A-tract increased with age, but heteroplasmy at the tRNA-Met site did not change with age. The finding of naturally occurring mtDNA heteroplasmy in an inbred strain of mouse makes the MRL mouse a powerful new experimental model for studies designed to explore therapeutic measures to alter the cellular burden of heteroplasmy.
MRL/MpJ小鼠是小家鼠的一种近交系实验室品系，已知其具有增强的自身免疫性、加快的伤口愈合能力和更强的再生特性。我们报道了MRL小鼠的全长线粒体DNA（mtDNA）序列（登录号# EU450583），并对两个自然发生的异质性位点的发现进行了表征。第一个是在甲硫氨酸转运RNA基因（tRNA-Met；mt-Tm）的TPsiC环中发生T3900C替换。第二个是在精氨酸转运RNA基因（tRNA-Arg；mt-Tr）的A序列（位于9821-9826位）中存在1-6个腺嘌呤核苷酸的异质性插入。在MRL个体中，这两个位点的异质性水平独立变化。tRNA-Arg的A序列长度随年龄增加，但tRNA-Met位点的异质性不随年龄变化。在近交系小鼠中发现自然发生的mtDNA异质性，使得MRL小鼠成为一种强大的新实验模型，可用于探索改变异质性细胞负荷的治疗措施的研究。
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