人类疾病建模是生物医学研究的重要组成部分，旨在了解其发病机制并最终开发治疗方法。在这里，我们将描述中枢神经系统肿瘤模型，重点关注内在的中枢神经系统肿瘤。早在 20 年代就建立了脑肿瘤模型系统，利用化学致癌作用和对不同致癌物的系统分析，并在 20 世纪 50 年代和 1960 年代进行了更精细的组织学分析。当时的替代方法使用逆转录病毒致癌作用，允许更局部、以器官为中心的递送。这种方法产生的大多数肿瘤是高级别神经胶质瘤。虽然这些实验方法没有直接证明细胞起源，但肿瘤的定位和生长模式已经指出了大脑神经源性区域的起源。在 20 世纪 80 年代，转基因模型中癌基因的表达允许通过在组织特异性启动子下表达转基因来实现更有针对性的方法，而肿瘤抑制基因的组成型失活（“敲除”）通常会导致胚胎致死。这个限制通过设计 Cre-lox 系统得到了很好的解决，允许启动子特异性的、通常也是时间控制的基因失活。最近，CRISPR Cas9 技术的使用显着提高了基因表达或基因失活的实验灵活性，从而增加了啮齿动物模型用于发病机制研究和建立临床前模型的价值。© 2024 作者。约翰·威利出版的《分子肿瘤学》

Modelling of human diseases is an essential component of biomedical research, to understand their pathogenesis and ultimately, develop therapeutic approaches. Here, we will describe models of tumours of the central nervous system, with focus on intrinsic CNS tumours. Model systems for brain tumours were established as early as the 1920s, using chemical carcinogenesis, and a systematic analysis of different carcinogens, with a more refined histological analysis followed in the 1950s and 1960s. Alternative approaches at the time used retroviral carcinogenesis, allowing a more topical, organ-centred delivery. Most of the neoplasms arising from this approach were high-grade gliomas. Whilst these experimental approaches did not directly demonstrate a cell of origin, the localisation and growth pattern of the tumours already pointed to an origin in the neurogenic zones of the brain. In the 1980s, expression of oncogenes in transgenic models allowed a more targeted approach by expressing the transgene under tissue-specific promoters, whilst the constitutive inactivation of tumour suppressor genes ('knock out')-often resulted in embryonic lethality. This limitation was elegantly solved by engineering the Cre-lox system, allowing for a promoter-specific, and often also time-controlled gene inactivation. More recently, the use of the CRISPR Cas9 technology has significantly increased experimental flexibility of gene expression or gene inactivation and thus added increased value of rodent models for the study of pathogenesis and establishing preclinical models.© 2024 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.