LSL-K-ras G12D Mice

Catalog Number: C001064

Strain Name: C57BL/6NCya-Krastm1(LSL-G12D)/Cya

Genetic Background: C57BL/6NCya

Reproduction: Heterozygote x WT

 

Strain Description

K-ras is a membrane-associated GTPase signal transduction protein that regulates proliferation, differentiation, and cell survival. Missense mutations at codon 12 result in decreased GTPase activity and constitutive signaling. Mutations in this gene occur in approximately 21% of all human cancers. This model carries a point mutation (G12D) and the gene expression is blocked by the presence of loxP-Stop-loxP, resulting in embryonic lethality in homozygotes. Cre-mediated recombination can excise the Stop element and allow expression of the K-ras gene carrying the point mutation. The mutational activation of K-ras can lead to aggressive cancers.

Strain Strategy


Figure 1. Gene editing strategy for LSL-K-ras G12D mice. A “loxP-PGK-Puro cassette (in reverse orientation)-Ad SA-4xSV40 pA-loxP” cassette was inserted into intron 1 of the mouse Kras gene, and the p.G12D (GGT to GAT) mutation was introduced into exon 2 of the mouse Kras gene.

 

Application

When this model is bred with tissue-specific Cre mice, the offspring can be used for studies of lesions in various tissues. For example, when bred with mice expressing Cre recombinase in melanocytes, these mutant mice may be useful in studying the development of melanoma.



References
[1]Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 2001 Dec 15;15(24):3243-8.
[2]O'Hagan RC, Heyer J. KRAS Mouse Models: Modeling Cancer Harboring KRAS Mutations. Genes Cancer. 2011 Mar;2(3):335-43.