FVB.B6(Cg)-Ddr2^{tm1d(EUCOMM)Wtsi}/GdlJ

Stock number: 031914
Product name: Ddr2^-
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Internal/Organ Research

Description

Ddr2^- ubiquitous null mice lack exon 8 of the discoidin domain receptor family, member 2 (Ddr2) gene, making these mice useful for studying tumor metastasis.

Detailed description

Ddr2^- ubiquitous null mice lack exon 8 of the discoidin domain receptor family, member 2 (Ddr2) gene. DDR2 is a collagen-induced receptor tyrosine kinase that activates pathways involved in cell adhesion, cell migration, proliferation, and extracellular matrix remodeling. This protein is expressed in numerous cell types, with high expression seen in mesenchymal cell and little to no expression seen in epithelial cell. DRD2 is also involved in wound repair and the regulation of tumor invasiveness. Mice that are heterozygous for this allele are viable and fertile, while homozygous mice are runted and sterile.

When bred with MMTV-PyMT (see Stock Numbers 002374 and 022974) expressing the Polyoma Virus middle T antigen under the direction of the mouse mammary tumor virus promoter, mice have no difference in primary tumor growth or total primary tumor burden compared to MMTV-PyMT Tg alone. They do, however, have a dramatic reduction in the number of macroscopic and microscopic metastases in the lungs with no difference in the average size of individual lung metastases.

Of note, the Ddr2^fl mice that retain the floxed exon 8 are available as Stock No. 031915.

Development

The L1L2_Bact_P cassette was inserted at a position on Chromosome 1 upstream of exon 8 of the discoidin domain receptor family, member 2 (Ddr2) gene. The cassette is composed of a frt site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second frt site and a second loxP site. A third loxP site was inserted downstream of exon 8. The construct, clone EDP0607_3, was purchased by Dr. Gregory Longmore (Washington University) and was introduced into C57BL/6N-A^tm1Brd-derived JM8A3.N1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric males were bred to FVB/NCrl mice. Subsequently these mice were bred to Flpo mice to remove the frt-flanked lacZ sequence and neomycin cassette. Resulting Ddr2^fl offspring were maintained on a mixed FVB/N;B6 genetic background and were further crossed to FVB/NCrl for at least 10 generations. This floxed strain is available as Stock No. 031914. Some of the floxed male mice were further crossed to Actin-Cre mice to remove exon 8. Resulting Ddr2^- ubiquitous null were bred to FVB/NCrl mice to remove the cre-expressing transgene and subsequently bred to FVB/NCrl mice for at least 10 generations. Cryopreserved sperm was sent to The Jackson Laboratory Repository. To establish our live colony, an aliquot of frozen sperm was used to fertilize FVB/NJ oocytes (Stock No. 001800).

Allele

Symbol: Ddr2^{tm1d(EUCOMM)Wtsi}
Name: targeted mutation 1d, Wellcome Trust Sanger Institute
MGI accession ID: MGI:6163489
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Ddr2
Marker name: discoidin domain receptor family, member 2
Marker synonyms: DDR2-N; MIG20a; Ntrkr3; TKT; Tyro10; WRCN
Chromosome: 1
Strain of origin: C57BL/6N-A^tm1Brd
Molecular note: The L1L2_Bact_P cassette was inserted at a position on Chromosome 1 upstream of exon 8.. The cassette is composed of an FRT site followed by lacZ sequence and a loxP site. This first loxP site is followed by neomycin under the control of the human beta-actin promoter, SV40 polyA, a second FRT site and a second loxP site. A third loxP site was inserted downstream of exon 8. Flp-mediated recombination removed the FRT-flanked neo cassette leaving exon 8 floxed. Cre-mediated recombination removed exon 8.