Matzuk M M, Bradley A
Institute for Molecular Genetics, Baylor College of Medicine, Houston, TX 77030.
Semin Cancer Biol. 1994 Feb;5(1):37-45.
The identification of cloning of tumor suppressor genes has mostly relied on familial human cancer predisposition syndromes and reverse genetics. Recent advances in our abilities to manipulate endogenous genes in the mouse by applying gene targeting techniques to ES cells has allowed animal models to be generated which have the same mutations as the human syndromes. Mice lacking one or both alleles of known tumor suppressor genes have been generated to evaluate the normal function of these genes. These animals have proven to be highly susceptible to tumor development, indicating that these mice are a potent in vivo assay system for tumor suppressor genes. The initiation of gonadal tumor development in mice lacking both copies of the alpha inhibin gene proved this assay and showed that inhibin is a novel tumor suppressor. Future identification of novel tumor suppressor genes will undoubtedly also include murine ES cell/gene targeting strategies for the identification and analysis of the function of these gene products in negative growth control.
肿瘤抑制基因的克隆鉴定大多依赖于家族性人类癌症易感综合征和反向遗传学。通过将基因靶向技术应用于胚胎干细胞来操纵小鼠内源基因的能力取得了新进展，这使得能够生成与人类综合征具有相同突变的动物模型。已经培育出缺乏已知肿瘤抑制基因一个或两个等位基因的小鼠，以评估这些基因的正常功能。这些动物已被证明对肿瘤发生高度敏感，这表明这些小鼠是一种用于肿瘤抑制基因的强大体内检测系统。缺乏α抑制素基因两个拷贝的小鼠性腺肿瘤的发生证实了这一检测方法，并表明抑制素是一种新型肿瘤抑制因子。未来新型肿瘤抑制基因的鉴定无疑还将包括利用小鼠胚胎干细胞/基因靶向策略来鉴定和分析这些基因产物在负生长调控中的功能。
