The Damaraland mole-rat (DMR; Fukomys damarensis) is a long-lived (~ 20 years) Bathyergid rodent that diverged 26 million years ago from its close relative, the naked mole-rat (NMR). While the properties of NMR cultured fibroblasts have been extensively studied and have revealed several unusual features of this cancer-resistant, long-lived species, comparative DMR studies are extremely limited. We optimized conditions for successfully culturing primary DMR skin fibroblasts and also established immortalized DMR cells using simian virus 40 early region expression. Like NMRs, DMR fibroblasts are more resistant than mice to various cytotoxins including heavy metals, DNA-damaging agents, oxidative stressors, and proteasome inhibitors. DMR genome sequencing analyses revealed the presence of premature stop codons in the master regulator genes of necroptosis, an inflammatory programmed cell death—receptor-interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like (MLKL), although these mutations have different locations to those found in the NMR. DMR cells, like NMR cells, did not show significantly increased cell death in response to necroptosis induction. Our data suggest that both Bathyergid species require species-specific cell culture conditions for optimized growth, display similar resistance to cytotoxins, and show loss-of-function mutations abrogating the ability to employ necroptosis. These shared traits may contribute to their evolved adaptations to their subterranean lifestyle and prolonged longevity. These convergent insights and valuable resource may be pertinent to biomedical research.

达马拉兰鼹鼠 （DMR;Fukomys damarensis）是一种长寿（~ 20 年）的深海啮齿动物，在 2600 万年前与它的近亲裸鼹鼠 （NMR） 分化。虽然 NMR 培养的成纤维细胞的特性已得到广泛研究，并揭示了这种抗癌、长寿物种的几个不寻常特征，但 DMR 的比较研究极其有限。我们优化了成功培养原代 DMR 皮肤成纤维细胞的条件，并使用猿猴病毒 40 早期区域表达建立了永生化 DMR 细胞。与 NMR 一样，DMR 成纤维细胞比小鼠对各种细胞毒素更具抵抗力，包括重金属、DNA 损伤剂、氧化应激源和蛋白酶体抑制剂。DMR 基因组测序分析显示，坏死性凋亡的主调节基因中存在过早终止密码子，坏死性凋亡是一种炎症性程序性细胞死亡-受体相互作用蛋白激酶 3 （RIPK3） 和混合谱系激酶结构域样 （MLKL），尽管这些突变的位置与 NMR 中发现的突变不同。DMR 细胞与 NMR 细胞一样，在坏死性凋亡诱导后没有显示细胞死亡显著增加。我们的数据表明，两种 Bathyergid 物种都需要物种特异性的细胞培养条件来优化生长，表现出对细胞毒素的相似抵抗力，并显示出功能丧失突变，从而消除了使用坏死性凋亡的能力。这些共同的特征可能有助于它们进化适应地下生活方式和延长寿命。这些趋同的见解和宝贵的资源可能与生物医学研究有关。