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.
