McCart Amy E, Vickaryous Nicola K, Silver Andrew
Colorectal Cancer Genetics Group, Institute of Cell and Molecular Science, Barts and The London, Queen Mary's School of Medicine and Dentistry, 4 Newark Street, Whitechapel, London E1 2AT, UK.
Pathol Res Pract. 2008;204(7):479-90. doi: 10.1016/j.prp.2008.03.004. Epub 2008 Jun 5.
The mouse provides an excellent in vivo system with which to model human diseases and to test therapies. Mutations in the Adenomatous polyposis coli (APC) gene are required to initiate familial adenomatous polyposis (FAP) and are also important in sporadic colorectal cancer tumorigenesis. The (multiple intestinal neoplasia Min) mouse contains a point mutation in the Apc gene, develops numerous adenomas and was the first model used to study the involvement of the Apc gene in intestinal tumorigenesis. The model has provided examples of modifying loci (called Modifiers of Min: Mom) in mice, demonstrating the principle of genetic modulation of disease severity. A spectrum of Apc mutant mice has since been developed, each with defining characteristics, some more able to accurately model human polyposis and colon cancer. We will focus our review on Apc mutant mouse models, the advent of models with concurrent or compound mutations and the importance of genetic background when modeling polyposis and cancer. Brief consideration will be given to the use of these models in drug testing.
小鼠提供了一个出色的体内系统，可用于模拟人类疾病和测试治疗方法。家族性腺瘤性息肉病（FAP）的发生需要腺瘤性息肉病 coli（APC）基因突变，并且在散发性结直肠癌的肿瘤发生中也很重要。（多发性肠道肿瘤 Min）小鼠在 Apc 基因中存在一个点突变，会发展出许多腺瘤，并且是第一个用于研究 Apc 基因在肠道肿瘤发生中作用的模型。该模型提供了小鼠中修饰位点（称为 Min 的修饰因子：Mom）的实例，证明了疾病严重程度的基因调控原理。此后开发了一系列 Apc 突变小鼠，每一种都有明确的特征，有些更能够准确模拟人类息肉病和结肠癌。我们将把综述重点放在 Apc 突变小鼠模型、并发或复合突变模型的出现以及在模拟息肉病和癌症时遗传背景的重要性上。还将简要考虑这些模型在药物测试中的应用。
