B6.129(Cg)-Chek1^tm1Jmr/J

Stock number: 019520
Research areas: Cancer Research, Research Tools

Description

Exon 2 of these Chek1 (checkpoint kinase 1) targeted mutant mice is flanked by loxP sites. When crossed with a tissue-specific Cre strain, the exon is excised, enabling selective disruption of protein production. This conditional allele may be helpful in the development of anticancer drug therapies.

Detailed description

Chek1 (checkpoint kinase 1) is a haploinsufficient tumor suppressor gene that is essential for embryonic stem cell survival. CHEK1 null mice reportedly exhibit embryonic lethality at E6.5 due to a peri-implantation defect. Activated CHEK1 prevents cell cycle progression by inhibiting the cell cycle phosphatases Cdc25a and Cdc25c.

Exon 2 of these targeted mutant mice is flanked by loxP sites. When crossed with a tissue-specific Cre strain, the exon is excised, enabling selective disruption of protein production.

When bred to mice carrying Tg(Wap-cre)11738Mam (see Stock No. 008735 for example), Cre recombinase expression in the mammary gland results in proliferating cells that undergo apoptosis leading to developmental defects. Conditional heterozygosity increases the number of S phase cells and causes spontaneous DNA damage.

This conditional allele may be helpful in the development of anticancer drug therapies.

Development

A loxP-flanked neomycin cassette was ligated to a 2.2 kb exon 2-containing genomic fragment, of which the last 59 bp was replaced by an EcoRV and a loxP site. The targeting vector was introduced to 129-derived embryonic stem (ES) cells and the neomycin marker was excised through transient expression of Cre recombinase. This strain was backcrossed to C57BL/6 an estimated 5-6 times by the donating laboratory (see SNP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 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 first generation rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome originated from an unknown source (chromosome 11 at ~8.40 Mbpand chromosome 13 at ~21.4 Mbp). In addition, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, suggesting the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Chek1^tm1Jmr
Name: targeted mutation 1, Jeffrey M Rosen
MGI accession ID: MGI:3046694
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Chek1
Marker name: checkpoint kinase 1
Chromosome: 9
Strain of origin: Not Specified
Molecular note: LoxP sites were inserted around a 2.2kb genomic segment containing exon 2 via homologous recombination.