p27S-/S- mutant mice contain a floxed-STOP cassette, blocking expression of p27Kit1. These mice may be useful for Cre-mediated rescue of p27Kit1 expression and subsequent tumor suppression.
Dr. Matthew Fero, Fred Hutchinson Cancer Research Center
p27S-/S- mutant mice contain a floxed-STOP cassette in the 5’ untranslated region of the cyclin-dependent kinase inhibitor 1B (Cdkn1b) gene, blocking expression of p27Kip1. 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 is associated with aggressive disease in a variety of cancer types in humans, including breast cancer, colon cancer, prostate cancer, and acute lymphoblastic leukemia (ALL). Homozygotes are viable and fertile, but females are infertile. They are larger than wildtype littermates, with thymus and spleen hyperplasia. They exhibit organ of Corti sensory cell hyperplasia, pituitary pars intermedia tumors. p27S-/S- mice also have shortened life spans and develop spontaneous pituitary tumors. After removal of the loxP-flanked STOP cassette via cre-mediated recombination, p27Kip1 expression is seen in all cells where Cre recombinase is expressed. When bred to mice expressing Cre Recombinase in the pars intermedia pituitary, p27Kip1 activation inhibits tumor development and prolongs survival.
A targeting vector was designed to insert a loxP-flanked neo STOP cassette in the 5’ untranslated region 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 chimeric mice were bred with 129S4 mice to generate p27S- 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 3, Matthew L Fero|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||p27S-; p27stop|
|Gene Symbol and Name||Cdkn1b, cyclin-dependent kinase inhibitor 1B|
|Strain of Origin||129S4/SvJaeSor|
|Molecular Note||A floxed transcriptional stop cassette was inserted into the 5' UTR. Protein was nearly undetectable in mutants.|
When maintaining a live colony, heterozygous females may be bred to homozygous males. The donating investigator reports that homozygous females are infertile.
When using the p27S- mouse strain in a publication, please cite the originating article(s) and include JAX stock #027329 in your Materials and Methods section.