Bmi1 is upregulated in a progressive manner in a wide variety of human tumors. Exons 4-8 of the mouse Bmi1 gene are flanked by loxP sites in this targeted allele. Cre-mediated excision of the floxed region results in a null allele.
Jacqueline A Lees, Koch Institute for Integrative Cancer Research at MIT
Bmi1 (Bmi1 polycomb ring finger oncogene) is a key transcriptional regulator in several organ stem cells and in cancer. Expression is upregulated in a progressive manner in a wide variety of human tumors, including colorectal cancer.
Exons 4-8 of the mouse Bmi1 gene are flanked by loxP sites in this targeted allele. Cre-mediated excision of the floxed region results in a null allele.
In a study of intestinal tumorigenesis, a conditional knockout of the Apc gene (Apc;Vil-cre) was combined with a germline knockout of Bmi1. In contrast to wild-type controls, compound mutant mice showed no increase in median tumor size, and a dramatic decrease in tumor number, between 3 and 4 months of age. As such, it is believed that the gene is required for both progression and maintenance of small intestinal adenomas.
An FRT-flanked neomycin resistance cassette was placed in intron 3, upstream of loxP sites inserted in introns 3 and 8. The mutation was created via homologous recombination in (C57BL/6 x 129S4/SvJae)F1-derived v6.5 embryonic stem (ES) cells. The selection cassette was subsequently deleted from resultant mice through crosses with a β-actin FLP mouse strain, leaving exons 4-8 were flanked by loxP sites. This strain was maintained on a mixed genetic background (involving 129S4/SvJae and C57BL/6, and possibly others) by the donating laboratory.
|Allele Name||targeted mutation 1.1, Jacqueline A Lees|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||Bmi1fl; Pcgf4|
|Gene Symbol and Name||Bmi1, Bmi1 polycomb ring finger oncogene|
|Strain of Origin||(C57BL/6 x 129S4/SvJae)F1|
|Molecular Note||An FRT flanked neo cassette was inserted in intron 3 upstream of loxP sites inserted in intron 3 and in intron 8. The selection cassette was subsequently deleted by crossing to a b-actin FLP mouse strain. Exons 4 to 8 were thus flanked by loxP sites.|
Homozygous and heterozygous floxed mice are viable and fertile. It has been noted that approximately 50% of initial homozygote x homozygote crosses at The Jackson Laboratory have been non-productive, however.
When using the Bmi1fl mouse strain in a publication, please cite the originating article(s) and include JAX stock #028572 in your Materials and Methods section.