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

我们发现，随着年龄的增长，mtDNA缺失的指数积累，而不是每个细胞的mtDNA拷贝数，在肌肉和大脑中的杂合敲入小鼠携带突变（D257 A）的mtDNA聚合酶（PolgA），CPEO和相关疾病的致病基因之一，往往伴随着情绪障碍。mtDNA缺失的组织特异性积累表明PolgA^<+/D257 A>小鼠适合作为CPEO的动物模型。PolgA^+/D257 A>小鼠通过常规行为测试组合未显示出行为变化，但显示出扭曲的昼夜节律。这种表型类似于在另一系突变小鼠中观察到的表型。线粒体DNA缺失的累积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.