MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS
MICE DEFICIENT FOR P53 ARE DEVELOPMENTALLY NORMAL BUT SUSCEPTIBLE TO SPONTANEOUS TUMORS
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DOI：
10.1038/356215a0
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发表时间：
1992-03-19
期刊：
影响因子：
64.8
通讯作者：
BRADLEY, A
中科院分区：
文献类型：
--
作者：
DONEHOWER, LA;HARVEY, M;BRADLEY, A
p53肿瘤抑制基因突变是人类癌症中最常见的遗传病变。为了研究p53基因在哺乳动物发育和肿瘤发生中的作用，在小鼠胚胎干细胞中通过同源重组将无效突变引入该基因。空等位基因纯合子小鼠表现正常，但在6月龄时易于自发发展各种肿瘤。这些观察结果表明，一个正常的p53基因是胚胎发育所必需的，它的缺乏使动物易患肿瘤性疾病，并且p53的致癌突变形式对于许多类型的肿瘤的发生不是强制性的。
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.