B6JOlaHsd.129P2-Ercc1^tm1Jhjh/J

Stock number: 040162
Product name: Ercc1-
Strain synonyms: B6JOlaHsd Ercc1-
Research areas: Cell Biology Research, Developmental Biology Research, Metabolism Research, Neurobiology Research

Description

Ercc1^- mice carry a targeted knock-out of the mouse Ercc1 (excision repair cross-complementing rodent repair deficiency, complementation group 1) gene. This is a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including liver, kidney, and the central nervous system (CNS).

Detailed description

Ercc1^- mice carry a targeted knock-out of the mouse Ercc1 (excision repair cross-complementing rodent repair deficiency, complementation group 1) gene. A neomycin cassette was introduced to the last coding exon (exon 7), preventing the essential expression of 74 essential carboxy terminal amino acids. Expression analysis shows an absence of transcript in mouse embryonic fibroblasts derived from homozygous mutant mice.

Ercc1^- homozygotes demonstrate retarded growth, enlarged liver nuclei, and greatly reduced lifespan (3-8 weeks). Homozygotes are born in reduced numbers (many dying by embryonic day 13.5) when bred on a pure C57BL/6 or FVB background. Therefore, experimental animals were only bred on a C57BL/6-FVB F1 genetic background by the donating laboratory. They exhibit an absence of subcutaneous fat, early onset of ferritin deposition in the spleen, kidney malfunction, gross abnormalities of ploidy, and cytoplasmic invaginations in nuclei of liver and kidney, and compromised nucleotide excision repair (NER) and cross-link repair. In addition, ERCC1-mutant cells undergo premature replicative senescence. Heterozygotes are not known to exhibit any phenotype. (Weeda, 1997; PMID 9197240)

This mutation is also available on a predominantly FVB genetic background (see Stock No. 040163), with homozygous animals reportedly surviving up to 10 weeks of age.

The donating laboratory wishes to note that all of their compound mutant experiments (PMID 27556946, PMID 36756698, PMID 38498063, PMID 22953029, PMID 38689513, PMID 38451018) were performed on an F1 hybrid genetic background. This hybrid background was derived from crosses of C57BL/6JOlaHsd-background mutant animals with FVB/NHanHsd-background mutant animals (e.g. Ercc1^+/- C57BL/6 x Ercc1^d/+ FVB (Stock No. 040165)). The contributing single mutant alleles were maintained independently through crosses of heterozygotes with C57BL/6JOlaHsd or FVB/NHanHsd inbred mice rather than wildtype animals from within their colonies (e.g. Ercc1^-/+ C57BL/6 x WT (Ercc1^+/+) C57BL/6). They did not maintain homozygous colonies and their F1 mice were not further intercrossed.

Development

A neomycin selection cassette, blocking the expression of 74 carboxy terminal amino acids, was introduced to exon 7 of the mouse Ercc1 gene via homologous recombination in 129P2/OlaHsd-derived E14 embryonic stem (ES) cells. The donating laboratory reported the resultant mice were backcrossed to C57BL/6JOlaHsd for more than 75 generations prior to sending heterozygous (Ercc1^-) females and wildtype C57BL/6JOlaHsd 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 C57BL/6J allele-type as previously observed for other B6JOlaHsd mouse lines.

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 99.4-99.8% of the markers consistent with C57BL/6JOlaHsd genetic background.

Allele

Symbol: Ercc1^tm1Jhjh
Name: targeted mutation 1, Jan H J Hoeijmakers
MGI accession ID: MGI:2183944
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Ercc1-
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
Molecular note: Exon 7 was disrupted by the insertion of a neomycin selection cassette. Expression analysis showed an absence of transcript in mouse embryonic fibroblasts derived from homozygous mutant mice. Further analysis showed that transcription of the antisense gene was unaffected by the targeting event.