Donehower L A, Harvey M, Slagle B L, McArthur M J, Montgomery C A, Butel J S, Bradley A
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030.
Nature. 1992 Mar 19;356(6366):215-21. doi: 10.1038/356215a0.
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours.
p53肿瘤抑制基因的突变是人类癌症中最常见的基因损伤。为了研究p53基因在哺乳动物发育和肿瘤发生中的作用,通过在小鼠胚胎干细胞中进行同源重组,将一个无效突变引入该基因。该无效等位基因的纯合小鼠看起来正常,但到6个月大时容易自发发生多种肿瘤。这些观察结果表明,正常的p53基因对于胚胎发育并非必需,其缺失使动物易患肿瘤性疾病,并且许多类型肿瘤的发生并不一定需要p53的致癌突变形式。