| First Author | McWhir J | Year | 1994 |
| Journal | Genet Res | Volume | 63 |
| Issue | 2 | Pages | 157 (Abstr.) |
| Mgi Jnum | J:18601 | Mgi Id | MGI:66863 |
| Citation | McWhir J, et al. (1994) Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Genet Res 63(2):157 (Abstr.) |
| abstractText | Full text of Abstract: Abstracts of papers. Mice with DNA repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. JIM McWHIR, JIM SELFRIDGE, DAVID J. HARRISON, SHOSHANA SQUIRES AND DAVID W. MELTON Institute of Cell and Molecular Biology, University of Edinburgh, Mayfield Road, Edinburgh EH9 3JR Nucleotide excision repair (NER) is one of the systems that has evolved to protect cells from the consequences of DNA damage. Defects in NER are associated with the hereditary human disease Xeroderma Pigmentosum which predisposes to skin cancer. The excision repair cross complementing gene (ERCC-1) was inactivated by gene targeting in the HPRT deficient embryonic stem cell line HM-1. Mice carrying this null allele was generated by blastocyst injection of the targeted ES cell line, followed by breeding from germline chimaeras. Primary cell lines isolated from ERCC-1 null embryos showed extremely low levels of NER. Genotyping of embryos at various stages post coitum showed that ERCC-1 deficiency did not compromise viability in utero. Homozygous ERCC-1 mutants were runted at birth and died prior to weaning with liver failure. Examination of organs revealed abnormal liver nuclear size in the perinatal period, progressing to severe aneuploidy by 3 weeks of age. Elevated levels of p53 could be detected by immuno- histochemistry in liver, kidney and brain of 3-week-old mice. This supports the hypothesized role for p53 as a monitor of DNA damage. This constitutes the first mouse model with a defined defect in any component of a mammalian NER system. |
