Mitochondrial DNA-depleter mouse as a model to study human pigmentary skin disorders.
Mitochondrial DNA-depleter mouse as a model to study human pigmentary skin disorders.
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线粒体dna耗尽小鼠作为研究人类色素皮肤疾病的模型。
DOI：
10.1111/pcmr.12921
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发表时间：
2021-03
影响因子：
4.3
通讯作者：
Singh, Keshav K.
中科院分区：
文献类型：
--
作者：
Villavicencio, Kyrene M.;Ahmed, Noha;Harris, Melissa L.;Singh, Keshav K.
色素异常在与衰老相关的表型谱和线粒体DNA耗竭综合征（MDS）患者中有报道。然而，一个相关的动物模型，模拟这些影响，并允许我们评估的黑素细胞功能的mtDNA耗竭的有害方面还没有描述。在这里，我们描述了在线粒体DNA耗竭小鼠的耳朵中观察到的色素变化，其表型包括附件周围假网络加重、斑片状色素沉着过度和色素沉着不足以及网状色素沉着。从组织学上看，这些小鼠表现出片状分布的表皮色素沉着增加，以及沿着增加且高度树枝状的黑素细胞。这些mtDNA缺失小鼠模拟了在患有与年龄相关的老年性雀斑样痣和MDS的人类中观察到的皮肤、色素变化的各个方面。我们认为，这种小鼠模型可以作为一个新的资源，为未来的审讯线粒体功能障碍如何有助于色素性皮肤病。mtDNA耗竭小鼠模型也可作为一种有用的工具，用于鉴定能够治疗人类与年龄相关的线粒体功能障碍相关的色素变化的新型药物。
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 periadnexal 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.
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影响因子：
10.3
作者：
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通讯作者：
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影响因子：
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4.3
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通讯作者：
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