Developmental studies of Brca1 and Brca2 knock-out mice
Developmental studies of Brca1 and Brca2 knock-out mice
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DOI：
10.1023/a:1018792200700
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发表时间：
1998-10-01
影响因子：
2.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
--
作者：
Hakem, R;de la Pompa, JL;Mak, TW
在人类中，乳腺癌易感基因 BRCA1 和 BRCA2 突变的遗传会增加患乳腺癌和卵巢癌的风险。为了研究它们的生物学功能并为这些癌症易感基因创建动物模型，通过基因打靶产生了同源基因 Brca1 和 Brca2 突变的几种小鼠品系。对这些“敲除”小鼠突变体的分析提供了有关这些基因功能的宝贵知识。 Brca1 和 Brca2 无效突变体在表型上相似：两个基因的突变都会导致胚胎致死，并且发育中的胚胎显示出与 p53 途径激活相关的细胞增殖缺陷的迹象。讨论了这种激活的重要性，以及这些癌症易感基因在 DNA 损伤修复中的作用。
In humans, the inheritance of mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 increases the risk of developing breast and ovarian cancer. To study their biological function and to create animal models for these cancer susceptibility genes, several strains of mice mutated in the homologous genes Brca1 and Brca2 have been generated by gene targeting. Analyses of these "knock-out" mouse mutants have provided invaluable knowledge about the function of these genes. Brca1 and Brca2 null mutants are similar in phenotype: mutations in both genes result in embryonic lethality and the developing embryos show signs of a cellular proliferation defect associated with activation of the p53 pathway. The significance of this activation, as well as the role of these cancer susceptibility genes in DNA damage repair, is discussed.