p27L+/L+ floxed mice possess loxP sites flanking the entire coding region of the cyclin-dependent kinase inhibitor 1B (Cdkn1b) gene. p27Kip1 is a regulator of cell cycle progression at G1 and is a tumor suppressor. Mutation in p27Kip1 have been linked to an increased risk for hereditary prostate cancer and multiple endocrine neoplasia (MEN) in humans. Decreased p27 expression associated with aggressive disease in a variety of cancer types in humans, including breast cancer, colon cancer, prostate cancer, and acute lymphoblastic leukemia (ALL). Mice that are homozygous for this allele are viable and fertile. They contain a moderate reduction of p27Kip1 RNA and protein levels. They are larger than wildtype littermates, with a larger thymus size. Homozygous females are fertile but with reduced fecundity. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have the entire coding region deleted in the cre-expressing tissues.
A targeting vector was designed to insert a loxP site upstream of the initiation site, and a frt-flanked neomycin resistance (neo) cassette, followed by a second loxP site, was inserted downstream of the stop codon of the cyclin-dependent kinase inhibitor 1B (Cdkn1b) gene. The construct was electroporated into 129S4/SvJaeSor-derived AK7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric mice were bred with 129S4/SvJaeSor-Gt(ROSA)26Sortm1(FLP1)Dym/J mice to delete the neo cassette. Progeny were crossed to remove the Flp-expressing transgene resulting in p27L+ mice on a pure 129S4 background. Upon arrival, mice were bred to 129S4/SvJaeJ inbred mice (Stock No. 009104) for at least one generation to establish the colony.
|Allele Name||targeted mutation 2, Matthew L Fero|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||p27L+; p27loxP|
|Gene Symbol and Name||Cdkn1b, cyclin-dependent kinase inhibitor 1B|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||LoxP sites were inserted to flank the locus. An FRT-flanked neo included in the vector was subsequently removed via flp mediated recombination. Protein was detected in mutants, but in moderately decreased amounts.|
When maintaining a live colony, homozygous mice may be bred together.
When using the p27L+ mouse strain in a publication, please cite the originating article(s) and include JAX stock #027328 in your Materials and Methods section.