Sci. Aging Knowl. Environ., 7 April 2004
Vol. 2004, Issue 14, p. tg2
GENETICALLY ALTERED MICE
Ercc1/ Mice (Ercc1tm1Dwm Mice)
||Ercc1/ Mice (Ercc1tm1Dwm Mice)
||129P2/OlaHsd; must breed heterozygotes because homozygous animals die before weaning.
||ERCC1 (excision repair cross-complementing rodent repair deficiency, complementation group 1)
|Type of change
||The neomycin resistance gene was inserted into exon 5.
|Nature of protein
||This protein forms a complex with ERCC4, ERCC11, and XP-F and is thought to be responsible for the 5' incision during DNA repair. The structure-specific ERCC1/XPF endonuclease complex that contains the ERCC1 and XPF subunits is implicated in the repair of two distinct types of lesions in DNA: (i) nucleotide excision repair (NER) for ultraviolet (UV)-induced lesions; and (ii) recombination repair of genotoxic interstrand cross-links.
||Homozygous ERCC1 null mice are runted at birth and die of liver failure before weaning. The perinatal liver displays polyploidy that develops to severe aneuploidy by 3 weeks of age, a condition generally associated with aging.
Transgenic expression of ERCC1 in the liver of such null mice results in increased life span. In this situation, both males and females are infertile, indicating a role for ERCC1 in spermatogenesis and oogenesis.
Two other ERCC1 mutant strains were shown to display defects in NER and cross-link repair. Additionally, cells derived from one of these strains exhibit premature replicative senescence.
|Corresponding human phenotype
||Although mutation of the murine homolog causes severe abnormalities, ERCC1 mutations have not been associated with any specific human diseases. However, NER defects are associated with xeroderma pigmentosum group F, a condition that is characterized by UV hypersensitivity, pigmentation abnormalities, and increased risk of skin cancer.
||J. McWhir, J. Selfridge, D. J. Harrison, S. Squires, D. W. Melton, Mice with DNA-repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nat. Genet. 5, 217-224 (1993).
||These mice are not commercially available. Please contact:
David W. Melton
Institute of Cell and Molecular Biology
Darwin Building, King's Buildings
Edinburgh EH9 3JR, Scotland, UK
For variant 1 (Ercc1tm1Jhjh) and variant 2 (Ercc1tm2Jhjh) mice, please contact:
Jan H. J. Hoeijmakers
Erasmus Universiteit Rotterdam
Vakgroep Celbiologie en Genetica
3000 DR Rotterdam
||There are two other strains in which the ERCC1 gene has been altered in some fashion: Ercc1tm1Jhjh and Ercc1tm2Jhjh mice.
Reference: G. Weeda, I. Donker, J. de Wit, H. Morreau, R. Janssens, C. J. Vissers, A. Nigg, H. van Steeg, D. Bootsma, J. H. J. Hoeijmakers, Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr. Biol. 7, 427-439 (1997).
||Related transgenic/knockout mice:
XPD (R722W) TTD
nucleotide excision repair
April 7, 2004
- K. T. Hsia, M. R. Millar, S. King, J. Selfridge, N. J. Redhead, D. W. Melton, P. T. Saunders, DNA repair gene Ercc1 is essential for normal spermatogenesis and oogenesis and for functional integrity of germ cell DNA in the mouse. Development 130, 369-378 (2003).[Abstract/Free Full Text]
- J. McWhir, J. Selfridge, D. J. Harrison, S. Squires, D. W. Melton, Mice with DNA-repair gene (ERCC-1) deficiency have elevated levels of p53, liver nuclear abnormalities and die before weaning. Nat. Genet. 5, 217-224 (1993).[CrossRef][Medline]
- G. Weeda, I. Donker, J. de Wit, H. Morreau, R. Janssens, C. J. Vissers, A. Nigg, H. van Steeg, D. Bootsma, J. H. J. Hoeijmakers, Disruption of mouse ERCC1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr. Biol. 7, 427-439 (1997).[CrossRef][Medline]
Mice). Sci. Aging Knowl. Environ. 2004
(14), tg2 (2004).