Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage.
Mouse Rad9b is essential for embryonic development and promotes resistance to DNA damage.
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小鼠 Rad9b 对于胚胎发育至关重要，并能促进对 DNA 损伤的抵抗力。
DOI：
10.1002/dvdy.22415
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发表时间：
2010
期刊：
影响因子：
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通讯作者：
Lieberman,HowardB
中科院分区：
文献类型：
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作者：
Leloup,Corinne;Hopkins,KevinM;Wang,Xiangyuan;Zhu,Aiping;Wolgemuth,DebraJ;Lieberman,HowardB
RAD9参与促进对DNA损伤的抗性、细胞周期检查点控制、DNA修复、细胞凋亡、胚胎发生和转录调控。RAD9(命名为RAD9B)的一个并列基因已被确定。为了确定Mrad9b(Mrad9b)的功能，构建了靶基因缺失的胚胎干细胞(ES)，并用于产生Mrad9b突变小鼠。Mrad9b−/−胚胎在E7.5后被吸收，而部分杂合子在E12.5到出生后几天内死亡。Mrad9bis在胚胎脑中表达，Mrad9b+/−胚胎表现出异常的神经管闭合。Mrad9b−/−小鼠胚胎成纤维细胞不能存活。Mrad9b−/−ES细胞对伽马射线和丝裂霉素C比Mrad9b+/+对照组更敏感，但表现出正常的伽马射线诱导的G2/M检查点控制。没有证据表明Mrad9b−/−细胞存在自发的基因组不稳定性。因此，我们的发现表明，Mrad9bis对胚胎发育是必不可少的，并介导了对某些DNA损伤剂的抗性。《发展动力学》239：2837-2850,2010。©2010 Wiley-Liss公司。
RAD9participates in promoting resistance to DNA damage, cell cycle checkpoint control, DNA repair, apoptosis, embryogenesis, and regulation of transcription. A paralogue ofRAD9(namedRAD9B) has been identified. To define the function of mouseRad9b(Mrad9b), embryonic stem (ES) cells with a targeted gene deletion were constructed and used to generateMrad9bmutant mice.Mrad9b−/−embryos are resorbed after E7.5 while some of the heterozygotes die between E12.5 and a few days after birth.Mrad9bis expressed in embryonic brain andMrad9b+/−embryos exhibit abnormal neural tube closure.Mrad9b−/−mouse embryonic fibroblasts are not viable.Mrad9b−/−ES cells are more sensitive to gamma rays and mitomycin C thanMrad9b+/+controls, but show normal gamma‐ray‐induced G2/M checkpoint control. There is no evidence of spontaneous genomic instability inMrad9b−/−cells. Our findings thus indicate thatMrad9bis essential for embryonic development and mediates resistance to certain DNA damaging agents. Developmental Dynamics 239:2837–2850, 2010. © 2010 Wiley‐Liss, Inc.