MICE WITH DNA-REPAIR GENE (ERCC-1) DEFICIENCY HAVE ELEVATED LEVELS OF P53, LIVER NUCLEAR ABNORMALITIES AND DIE BEFORE WEANING
MICE WITH DNA-REPAIR GENE (ERCC-1) DEFICIENCY HAVE ELEVATED LEVELS OF P53, LIVER NUCLEAR ABNORMALITIES AND DIE BEFORE WEANING
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DOI：
10.1038/ng1193-217
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发表时间：
1993-11-01
期刊：
影响因子：
30.8
通讯作者：
MELTON, DW
中科院分区：
文献类型：
--
作者：
MCWHIR, J;SELFRIDGE, J;MELTON, DW
核苷酸切除修复的缺陷与易患皮肤癌的人类着色性干皮病有关。通过靶向胚胎干细胞系HM-1中的切除修复交叉互补基因（ERCC-1）产生DNA修复缺陷小鼠。纯合子ERCC-1突变体在出生时发育不良，并在断奶前死于肝功能衰竭。器官检查显示围产期肝脏为多倍体，3周龄时发展为严重的非整倍体。在肝脏、大脑和肾脏中检测到p53水平升高，支持了p53作为DNA损伤监测器的假设作用。
Defects in nucleotide excision repair are associated with the human condition xeroderma pigmentosum which predisposes to skin cancer. Mice with defective DNA repair were generated by targeting the excision repair cross complementing gene (ERCC-1) in the embryonic stem cell line, HM-1. Homozygous ERCC-1 mutants were runted at birth and died before weaning with liver failure. Examination of organs revealed polyploidy in perinatal liver, progressing to severe aneuploidy by 3 weeks of age. Elevated p53 levels were detected in liver, brain and kidney, supporting the hypothesised role for p53 as a monitor of DNA damage.