Research of the relationship between accumulation of mtDNA deletions and bipolar disorder in an animal model

我们发现，携带mtDNA聚合酶（PolgA）突变（D257A）的杂合敲入小鼠的肌肉和大脑中，mtDNA缺失的指数积累随着年龄的增长而增强，而不是每个细胞的mtDNA拷贝数，PolgA是CPEO和相关疾病的致病基因之一，通常伴随情绪障碍。mtDNA缺失的组织特异性积累表明，PolgA^<+/D257A>小鼠适合用于CPEO动物模型。PolgA^<+/D257A>小鼠未表现出常规行为测试电池的行为改变，但表现出昼夜节律扭曲。这种表型与另一种突变小鼠的表型相似。mtDNA缺失的积累有可能导致情绪障碍。

We found that exponential accumulation of mtDNAs deletions with ageing, but not mtDNA copy number per cell, are enhanced in muscles and the brains of heterozygous knock-in mice carrying a mutation (D257A) in mtDNA polymerase (PolgA), one of the causative genes of CPEO and related diseases, which often accompany mood disorder. Tissue-specific accumulation of mtDNA deletions suggests that PolgA^<+/D257A> mice are suitable for an animal model of CPEO. PolgA^<+/D257A> mice did not show behavioural changes by conventional behavioural test battery, but showed distorted day-night rhythm. This phenotype resembled the phenotype seen in the other line of mutant mice. There is possibility that accumulation of mtDNA deletions causes mood disorders.