This mouse line was developed in the laboratory of Jos Jonkers of the Netherlands Cancer Institute (NKI). The Invasive Lobular Breast Cancer Model was developed by mating conditional Trp53 mice with K14Cre transgenic mice, and the resultant offspring were crossed with conditional Cdh1 mice. The conditional Cdh1 mouse was generated by injection of 129P2-derived E14 IB10 ES cells containing a targeted Cdh1 allele with floxed exons 4-15 into C57BL/6 blastocysts. Resultant chimeras were crossed with FVB/N mice to produce outbred heterozygous offspring (Derksen 2006). The conditional Trp53 mouse was generated by targeting a 13.5 kb genomic clone encompassing Trp53 exons 1-11 in 129P2-derived ES cells of the E14 subclone IB10. Targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeras were crossed with FVB/N mice to produce outbred heterozygous offspring (Jonkers 2001). The K14cre transgenic mice were derived by pronuclear injection of the transgene into FVB/N one cell-stage embryos according to standard procedures. The K14cre transgene includes a 2.1 kb human K14 gene promoter fragment followed by a 0.65 kb rabbit β-globin intron, the Cre coding sequences and a 0.63-kb transcription termination/polyadenylation fragment of the human growth hormone gene (Jonkers 2001). This model was backcrossed to the FVB strain prior to receipt at Taconic, and SNP testing shows this model to be congenic on the FVB inbred background at NE8.
Taconic received stock in 2011, and the line was derived by embryo transfer. The colony was maintained by mating females which are homozygous for both of the floxed genes and wild type for the Cre with males which are homozygous for both of the floxed genes and carriers for the Cre.
Jonkers J, Meuwissen R, van der Gulden H, Peterse H, van der Valk M and Berns A. (2001). Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat Genet 29, 418-425.
Derksen PW, Liu X, Saridin F, van der Gulden H, Zevenhoven J, Evers B, van Beijnum JR, Griffioen AW, Vink J, Krimpenfort P, Peterse JL, Cardiff RD, Berns A, Jonkers J. (2006) Somatic inactivation of E-cadherin and p53 in mice leads to metastatic lobular mammary carcinoma through induction of anoikis resistance and angiogenesis. Cancer Cell, 10(5):347-349.
Additional Publication:
Warmoes M, Jaspers JE, Xu G, Sampadi BK, Pham TV, Knol JC, Piersma SR, Boven E, Jonkers J, Rottenberg S, Jimenez CR. (2013) Proteomics of genetically engineered mouse mammary tumors identifies fatty acid metabolism members as predictive markers for cisplatin resistance. Mol Cell Proteomics. Feb 8.