FVBNHanHsd.129P2-Ercc1^tm2Dwm/IvdpJ

Stock number: 040166
Product name: Ercc1^fl , Ercc1^flox
Strain synonyms: FVBNHanHsd Ercc1^flox
Research areas: Neurobiology Research, Research Tools

Description

Ercc1^flox mice carry a conditional mutant allele in which exons 3-5 of the mouse Ercc1 (excision repair cross-complementing rodent repair deficiency, complementation group 1) gene are flanked by loxP sites. This strain is useful to study tissue-specific effects of DNA repair deficiency.

Detailed description

Ercc1 (excision repair cross-complementing rodent repair deficiency, complementation group 1) has an essential role in the nucleotide excision repair (NER) pathway that protects against ultraviolet (UV)-induced DNA damage. It is also involved in homologous recombination, double-strand break repair, and the repair of interstrand crosslinks. Mice that are deficient in this protein are born severely runted and die by ~3 weeks of age with liver failure on a C57BL/6 genetic background (viable on a mixed FVB-C57BL/6 background). Premature hepatocyte polyploidy is reminiscent of a premature aging disorder.

Ercc1^flox mice carry a conditional mutant allele in which exons 3-5 of the mouse Ercc1 gene are flanked by loxP sites. Cre recombinase-mediated excision of the floxed region results in a knock-out allele.

Development

In the first round of gene targeting, exons 3-5 of the mouse Ercc1 gene were replaced with an Hprt minigene to inactivate Ercc1 in 129P2/OlaHsd-Hprt1^b-m3-derived HM-1 Hprt-deficient embryonic stem (ES) cells. In the second round, the Hprt marker in the knock-out clone was replaced with the Ercc1 exon 3-5 region flanked by loxP sites. The donating laboratory reported the resultant mice were backcrossed to FVB/NHanHsd for more than 75 generations prior to sending heterozygous (Ercc1^flox) females and wildtype FVB/NHanHsd males to The Jackson Laboratory in 2025. Upon arrival, those females and males were used to rederive the colony. Subsequently, embryos will be cryopreserved.

In 2025, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the heterozygous females and wildtype males sent to The Jackson Laboratory. All markers were FVB/N allele-type.

In 2025, heterozygous females and wildtype males were sent to The Jackson Laboratory. One heterozygous female and one wildtype male from that cohort were analyzed via the miniMUGA 10,000 SNP panel. This showed 97.5-99.9% of the markers consistent with FVB/N genetic background. These data suggest the mice sent to The Jackson Laboratory were on an FVB/N-congenic genetic background.

Allele

Symbol: Ercc1^tm2Dwm
Name: targeted mutation 2, David W Melton
MGI accession ID: MGI:3692923
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Synonyms: Ercc1^flox
Marker symbol: Ercc1
Marker name: excision repair cross-complementing rodent repair deficiency, complementation group 1
Marker synonyms: COFS4; Ercc-1; RAD10; UV20
Chromosome: 7
Strain of origin: 129P2/OlaHsd-Hprt1^b-m3
Molecular note: In the first step of a two step process, exons 3-5 were replaced with an Hprt minigene. In the second step, the Hprt1 marker was replaced with the Ercc1 exons 3-5 region flanked by loxP sites.