Brca2 is required for embryonic cellular proliferation in the mouse
Brca2 is required for embryonic cellular proliferation in the mouse
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DOI：
10.1101/gad.11.10.1242
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发表时间：
1997-05-15
影响因子：
10.5
通讯作者：
Mak, TW
中科院分区：
文献类型：
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作者：
Suzuki, A;delaPompa, JL;Mak, TW
肿瘤抑制基因 BRCA2 的突变与乳腺癌和其他癌症的易感性有关。通过基因靶向删除 Brca2 基因外显子 10 和 11 的纯合突变小鼠 (Brca2(10-11)) 在胚胎发生第 9.5 天之前死亡。突变体表型范围从不能原肠胚形成的严重发育迟缓胚胎到尺寸减小的胚胎，形成中胚层并存活到发育 8.5 天。虽然细胞凋亡是正常的，但 Brca2(10-11) 突变体的细胞增殖在体内和体外均受到损害。此外，细胞周期蛋白依赖性激酶抑制剂p21的表达增加。因此，Brca2(10-11)突变体的表型与Brca1(5-6)突变体相似，但受影响程度较轻。这两个基因中的任何一个的表达在另一个基因的突变胚胎中不受影响。这项研究表明，Brca2 与 Brca1 一样，是胚胎发生过程中细胞增殖所必需的。 Brca1 和 Brca2 突变体之间表型的相似性表明这些基因在胚胎发生过程中可能具有协同作用或趋同功能。
Mutations of the tumor suppressor gene BRCA2 are associated with predisposition to breast and other cancers. Homozygous mutant mice in which exons 10 and 11 of the Brca2 gene were deleted by gene targeting (Brca2(10-11)) die before day 9.5 of embryogenesis. Mutant phenotypes range from severely developmentally retarded embryos that do not gastrulate to embryos with reduced size that make mesoderm and survive until 8.5 days of development, Although apoptosis is normal, cellular proliferation is impaired in Brca2(10-11) mutants, both in vivo and in vitro. In addition, the expression of the cyclin-dependent kinase inhibitor p21 is increased. Thus, Brca2(10-11) mutants are similar in phenotype to Brca1(5-6) mutants but less severely affected. Expression of either of these two genes was unaffected in mutant embryos of the other. This study shows that Brca2, like Brca1, is required for cellular proliferation during embryogenesis. The similarity in phenotype between Brca1 and Brca2 mutants suggests that these genes may have cooperative roles or convergent functions during embryogenesis.