This targeted mutation of the cyclin-dependent kinase inhibitor 1B (Cdkn1b) gene develops fewer urethane-induced lung tumors and may be useful in studies of cell cycle regulation and tumor suppression.
James Roberts, Fred Hutchinson Cancer Research Center
Genetic Background | Generation |
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Allele Type | Gene Symbol | Gene Name |
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Targeted | Cdkn1b | cyclin-dependent kinase inhibitor 1B |
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This amino acid substitution in the Cdkn1b (p27) phosphorylation site results in an increased association of p27 with cyclin and cyclin dependent kinase complexes. In addition, mice exhibit a reduced susceptibility to urethane-induced lung tumors as compared to wild-type and p27 null mice, suggesting a function for phosphorylation of p27 in the regulation of tumor suppression.
The targeting vector was designed (by site-directed mutagenesis) to change the main phosphorylation site found in the murine Cdkn1b cDNA sequence from a serine to alanine at amino acid position 10 (S10A). A loxP-flanked neomycin cassette was also inserted upstream of exon 2. The construct was electroporated into 129S4/SvJaeSor derived AK7.1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to mice carrying Meox2tm1(cre)Sor to remove the neo cassette. Mice were crossed to C57BL/6 for one generation and then to 129S4/SvJaeSor. Genome scan analysis provided by the donating investigator indicated that this strain has a genetic background that is composed of 0.96875% 129 and 0.03125% C57BL/6.
Allele Name | targeted mutation 2, James M Roberts |
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Allele Type | Targeted |
Allele Synonym(s) | P27S10A |
Gene Symbol and Name | Cdkn1b, cyclin-dependent kinase inhibitor 1B |
Gene Synonym(s) | |
Strain of Origin | 129S4/SvJaeSor |
Chromosome | 6 |
Molecular Note | The main phosphorylation site was changed from serine to alanine at amino acid position 10 by homologous recombination. |
Mutations Made By | James Roberts, Fred Hutchinson Cancer Research Center |
While maintaining a live colony, these mice are bred as homozygotes.
When using the 129S4(B6)-Cdkn1btm2Jro/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010834 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous for Cdkn1b<tm2Jro> |
Frozen Mouse Embryo | 129S4(B6)-Cdkn1b<tm2Jro>/J | $2595.00 |
Frozen Mouse Embryo | 129S4(B6)-Cdkn1b<tm2Jro>/J | $2595.00 |
Frozen Mouse Embryo | 129S4(B6)-Cdkn1b<tm2Jro>/J | $3373.50 |
Frozen Mouse Embryo | 129S4(B6)-Cdkn1b<tm2Jro>/J | $3373.50 |
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