瘤抑制基因Brca1对于小鼠的胚胎细胞增殖是必要的
R Hakem1, J L de la Pompa, C Sirard
1Amgen Institute, Toronto, Ontario, Canada.
Cell
|June 28, 1996
概括
BRCA1基因的突变与癌症有关. 同卵性Brca1突变小鼠胚胎无法正常发育,并且由于细胞增殖受损,在胚胎发生的早期死亡.
科学领域:
- 发育生物学是发展生物学.
- 遗传学 是一个遗传学.
- 癌症研究 癌症研究
背景情况:
- BRCA1基因的突变与人类遗传性乳腺癌和卵巢癌有关.
- Brca1+/-小鼠是可活的,在11个月大时不会发展成瘤.
研究的目的:
- 为了研究同卵性Brca1突变的胚胎致死性.
- 了解Brca1突变体胚胎发育缺陷背后的细胞机制.
主要方法:
- 生产和分析同卵性Brca1(5-6) 突变小鼠.
- 胚胎发育的体内和体外研究,包括细胞增殖和细胞亡分析.
- 对基因表达的分析,包括环林E,mdm-2和p21.
主要成果:
- 同卵性Brca1(5-6) 突变胚胎在胚胎发生的第7.5天之前表现出发育失败,中皮形成受损和异常的胚胎外发育.
- 突变胚胎显示细胞增殖减少和循环素E和mdm-2的表达减少,p21表达急剧增加.
- 在体外研究证实了突变胚胎中的严重损伤的胚胎细胞生长.
结论:
- 在胃化之前,Brca1(5-6) 突变小鼠的胚胎致死率可能是由生殖层发育所必需的繁殖突破失败引起的.
- 在早期胚胎细胞增殖和发育中,BRCA1起着至关重要的作用,独立于它在与癌症倾向相关的DNA修复中的作用.
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