Telomeres protect the ends of chromosomes but shorten following cell division in the absence of telomerase activity. When telomeres become critically short or damaged, a DNA damage response is activated. Telomeres then become dysfunctional and trigger cellular senescence or death. Telomere shortening occurs with ageing and may contribute to associated maladies such as infertility, neurodegeneration, cancer, lung dysfunction and haematopoiesis disorders. Telomere dysfunction (sometimes without shortening) is associated with various diseases, known as telomere biology disorders (also known as telomeropathies). Telomere biology disorders include dyskeratosis congenita, Høyeraal–Hreidarsson syndrome, Coats plus syndrome and Revesz syndrome. Although mouse models have been invaluable in advancing telomere research, full recapitulation of human telomere-related diseases in mice has been challenging, owing to key differences between the species. In this Review, we discuss telomere protection, maintenance and damage. We highlight the differences between human and mouse telomere biology that may contribute to discrepancies between human diseases and mouse models. Finally, we discuss recent efforts to generate new ‘humanized’ mouse models to better model human telomere biology. A better understanding of the limitations of mouse telomere models will pave the road for more human-like models and further our understanding of telomere biology disorders, which will contribute towards the development of new therapies.

端粒保护染色体的末端，但在没有端粒酶活性的情况下，细胞分裂后会缩短。当端粒变得严重短或受损时，DNA 损伤反应被激活。端粒随后变得功能失调并引发细胞衰老或死亡。端粒缩短会随着年龄的增长而发生，并可能导致相关疾病，例如不孕症、神经退化、癌症、肺功能障碍和造血障碍。端粒功能障碍（有时没有缩短）与各种疾病有关，称为端粒生物学疾病（也称为端粒病）。端粒生物学疾病包括先天性角化不良、Høyeraal-Hreidarsson 综合征、Coats plus 综合征和 Revesz 综合征。尽管小鼠模型在推进端粒研究方面具有不可估量的价值，但由于物种之间的关键差异，在小鼠中完全概括人类端粒相关疾病一直具有挑战性。在这篇评论中，我们讨论了端粒的保护、维护和损伤。我们强调了人类和小鼠端粒生物学之间的差异，这些差异可能导致人类疾病和小鼠模型之间的差异。最后，我们讨论了最近为生成新的“人源化”小鼠模型以更好地模拟人类端粒生物学所做的努力。更好地了解小鼠端粒模型的局限性将为更多类似人类的模型铺平道路，并进一步了解端粒生物学疾病，这将有助于新疗法的开发。