R26loxpTA-p57 mice allow Cre recombinase-inducible expression of the cell cycle inhibitor p57Kip2 (Cdkn1c), resulting in cell cycle arrest in G1 phase of the cre expressing cells.
James F Padbury, Women & Infants Hospital of Rhode Island
Genetic Background | Generation |
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|
Allele Type | Gene Symbol | Gene Name |
---|---|---|
Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) | Gt(ROSA)26Sor | gene trap ROSA 26, Philippe Soriano |
The R26loxpTA-p57 allele has a loxP-flanked transcriptional termination cassette upstream of a mouse p57Kip2 (Cdkn1c) cDNA sequence, all inserted into the Gt(ROSA)26Sor locus. Although under control of the Gt(ROSA)26Sor promoter, widespread expression of p57Kip2 is prevented by the upstream floxed-STOP cassette in the absence of Cre recombinase. Heterozygous mice (R26loxpTA-p57k/+) are viable and fertile with no reported phenotypic abnormalities. The donating investigator reports that homozygous mice (R26loxpTA-p57k/k) have the same phenotype as heterozygous mice.
When bred to mice that express Cre recombinase, offspring will have the floxed-STOP cassette deleted in cre-expressing cells; resulting in p57Kip2 expression and subsequent cell cycle inhibition/arrest in G1 phase.
For example, when R26loxpTA-p57 mice are bred with mice expressing Cre recombinase in myocardial cells (Mlc2v-Cre knockin), the myocardial specific p57Kip2 expression in the embryonic and adult ventricular cardiomyocytes attenuates hypoxic-ischemic injury.
The R26loxp-TAp57 targeting sequence was designed with (from 5' to 3')
a splice acceptor,
a loxP-flanked strong transcriptional termination sequence (PGK-neo-polyA [tpA]),
a 1.4 kbp cDNA containing the complete open reading frame of mouse p57Kip2 (Cdkn1c),
and a bovine polyA signal.
The p57Kip2 sequence encodes the mouse Cdkn1c [cyclin-dependent kinase inhibitor 1C (P57)] protein that functions as a cell cycle inhibitor by binding to G1 cyclin-CDK complexes and causing arrest of the cell cycle in G1 phase.
The R26loxp-TAp57 construct was inserted between exons 1 and 2 of the Gt(ROSA)26Sor locus on chromosome 6 via electroporation of 129S7/SvEvBrd-Hprtb-m2 derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6-Tyrc-Brd females to obtain F1 progeny. The resulting R26loxpTA-p57 mice were maintained on a mixed C57BL/6;129/Sv background prior to sending to The Jackson Laboratory in 2009. Upon arrival, sperm was cryopreserved. To generate our living R26loxpTA-p57 mouse colony, an aliquot of the frozen sperm was used to fertilize oocytes from C57BL/6J females (Stock No. 000664).
Expressed Gene | Cdkn1c, cyclin-dependent kinase inhibitor 1C (P57), mouse, laboratory |
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Site of Expression |
Allele Name | targeted mutation 1, James Padbury |
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Allele Type | Targeted (Conditional ready (e.g. floxed), Inserted expressed sequence) |
Allele Synonym(s) | Gt(ROSA)26Sortm1(xstpx-Cdkn1c)Jfpa; R26loxpTA-p57; R26loxpTA-p57k; R26loxpTA-p57Kip2 |
Gene Symbol and Name | Gt(ROSA)26Sor, gene trap ROSA 26, Philippe Soriano |
Gene Synonym(s) | |
Expressed Gene | Cdkn1c, cyclin-dependent kinase inhibitor 1C (P57), mouse, laboratory |
Strain of Origin | 129S7/SvEvBrd-Hprtb-m2 |
Chromosome | 6 |
Molecular Note | A 1.4 kb cDNA containing the complete open reading frame of the mouse gene was placed under the control of a loxP-flanked transcriptional termination sequence. This construct was inserted betweenexons 1 and 2. |
When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony, or to C57BL/6J inbred mice (Stock No. 000664). The donating investigator reports that homozygous mice (R26loxpTA-p57k/k) have the same phenotype as heterozygous mice.
When using the R26loxpTA-p57k mouse strain in a publication, please cite the originating article(s) and include JAX stock #022516 in your Materials and Methods section.
Facility Barrier Level Descriptions
Service/Product | Description | Price |
---|---|---|
Heterozygous or wildtype for Gt(ROSA)26Sor<tm1(Cdkn1c)Jfpa> |
Frozen Mouse Embryo | B6;129S-Gt(ROSA)26Sor<tm1(Cdkn1c)Jfpa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S-Gt(ROSA)26Sor<tm1(Cdkn1c)Jfpa>/J Frozen Embryo | $2595.00 |
Frozen Mouse Embryo | B6;129S-Gt(ROSA)26Sor<tm1(Cdkn1c)Jfpa>/J Frozen Embryo | $3373.50 |
Frozen Mouse Embryo | B6;129S-Gt(ROSA)26Sor<tm1(Cdkn1c)Jfpa>/J Frozen Embryo | $3373.50 |
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