McWhir J, Selfridge J, Harrison DJ, Squires S, Melton DW:
Mice with DNA repair gene (ERCC-1) deficiency have elevated levels
of p53, liver nuclear abnormalities and die before weaning.
Nature Genetics 1993 Nov;5(3):217-24
ABSTRACT
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.
