Cdkn2a-LSL-P2A-DTR-T2A-tdTomato Mouse
Product Name
Cdkn2a-LSL-P2A-DTR-T2A-tdTomato Mouse
Product ID
C002201
Strain Name
C57BL/6Cya-Cdkn2aem1(LSL-P2A-DTR-T2A-tdTomato)/Cya
Background
C57BL/6Cya
Examples of Expressing Tissues/Cells
Senescence-associated cells, tumor cells, and other Cdkn2a-positive cells
Status
When using this mouse strain in a publication, please cite “Cdkn2a-LSL-P2A-DTR-T2A-tdTomato Mouse (Catalog C002201) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Standard products are sold as live mice derived from cryorecovery or expansion. Frozen materials are available upon request. Pricing and lead times depend on real-time inventory.
Gene Name
Cdkn2a
Gene Alias
Arf, p16, MTS1, Pctr1, p19ARF, p16INK4a, p19<ARF>, ARF-INK4a, INK4a-ARF, Ink4a/Arf, p16(INK4a)
NCBI ID
Chromosome
Chr 4 (Mouse)
MGI ID
Datasheet
Strain Description
The Cdkn2a (cyclin-dependent kinase inhibitor 2A) gene encodes proteins including p16INK4a and plays an important role in cell cycle regulation and cellular senescence. p16INK4a is one of the commonly used markers of cellular senescence. It is expressed in various tissues and cell types and can be upregulated during senescence, injury, or cellular stress [1-3].
In this model, the endogenous stop codon of the mouse Cdkn2a gene was replaced with the loxP-AA-6×SV40 pA-loxP-TG-P2A-DTR-T2A-tdTomato expression cassette using gene-editing technology. The p16 transcript can theoretically continue translation into the loxP sequence, resulting in an additional amino acid sequence at the C-terminus, followed by a new termination signal formed by the inserted “AA” sequence. Following Cre-mediated excision of the LSL element, the endogenous Cdkn2a regulatory elements drive the expression of DTR (diphtheria toxin receptor) and tdTomato fluorescent protein. Cdkn2a-positive cells express tdTomato, and subsequent administration of diphtheria toxin (DT) selectively depletes DTR-expressing cells. DTR and tdTomato are expected to be expressed in senescence-associated cells, tumor cells, and other Cdkn2a-positive cells.
Reference
Krishnamurthy, J., Torrice, C., Ramsey, M. R., Kovalev, G. I., Al-Regaiey, K., Su, L., & Sharpless, N. E. (2004). Ink4a/Arf expression is a biomarker of aging. The Journal of clinical investigation, 114(9), 1299–1307.
Gorgoulis, V., Adams, P. D., Alimonti, A., Bennett, D. C., Bischof, O., Bishop, C., Campisi, J., Collado, M., Evangelou, K., Ferbeyre, G., Gil, J., Hara, E., Krizhanovsky, V., Jurk, D., Maier, A. B., Narita, M., Niedernhofer, L., Passos, J. F., Robbins, P. D., Schmitt, C. A., … Demaria, M. (2019). Cellular Senescence: Defining a Path Forward. Cell, 179(4), 813–827.
Suryadevara, V., Hudgins, A. D., Rajesh, A., Pappalardo, A., Karpova, A., Dey, A. K., Hertzel, A., Agudelo, A., Rocha, A., Soygur, B., Schilling, B., Carver, C. M., Aguayo-Mazzucato, C., Baker, D. J., Bernlohr, D. A., Jurk, D., Mangarova, D. B., Quardokus, E. M., Enninga, E. A. L., Schmidt, E. L., … Neretti, N. (2024). SenNet recommendations for detecting senescent cells in different tissues. Nature reviews. Molecular cell biology, 25(12), 1001–1023.
Strain Strategy
The endogenous stop codon of the mouse Cdkn2a gene was replaced with the loxP-AA-6×SV40 pA-loxP-TG-P2A-DTR-T2A-tdTomato expression cassette.
Figure 1. Gene editing strategy for Cdkn2a-LSL-P2A-DTR-T2A-tdTomato mice.
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