Pigmentation abnormalities are reported in the spectrum of phenotypes associated with aging and in patients with mitochondrial DNA depletion syndrome (MDS). Yet, a relevant animal model that mimics these effects and would allow us to evaluate the detrimental aspects of mtDNA depletion on melanocyte function has not been described. Here, we characterize the pigmentary changes observed in the ears of a mtDNA‐depleter mouse, which phenotypically includes accentuation of the peri‐adnexal pseudonetwork, patchy hyper‐ and hypopigmentation, and reticular pigmentation. Histologically, these mice show increased epidermal pigmentation with patchy distribution, along with increased and highly dendritic melanocytes. These mtDNA‐depleter mice mimic aspects of the cutaneous, pigmentary changes observed in humans with age‐related senile lentigines as well as MDS. We suggest that this mouse model can serve as a novel resource for future interrogations of how mitochondrial dysfunction contributes to pigmentary skin disorders. The mtDNA‐depleter mouse model also serves as a useful tool to identify novel agents capable of treating pigmentary changes associated with age‐related mitochondrial dysfunction in humans.

中文翻译：

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线粒体 DNA 耗竭小鼠作为研究人类色素性皮肤病的模型

在与衰老相关的表型谱和线粒体 DNA 耗竭综合征 (MDS) 患者中报告了色素沉着异常。然而，尚未描述模拟这些影响并允许我们评估 mtDNA 消耗对黑素细胞功能的不利方面的相关动物模型。在这里，我们描述了在 mtDNA 耗竭小鼠耳朵中观察到的色素变化，其表型包括附件周围假网络的加重、斑片状色素沉着过度和色素减退以及网状色素沉着。组织学上，这些小鼠表现出增加的表皮色素沉着和斑片状分布，以及增加和高度树突状的黑色素细胞。这些 mtDNA 耗竭小鼠模拟了在患有与年龄相关的老年斑和 MDS 的人类中观察到的皮肤、色素变化的各个方面。我们建议这种小鼠模型可以作为未来研究线粒体功能障碍如何导致色素性皮肤病的新资源。mtDNA 耗竭小鼠模型还可以作为一种有用的工具来识别能够治疗与人类年龄相关的线粒体功能障碍相关的色素变化的新药物。