B6.129(Cg)-Cdcp1^tm1.2Moas/J

Stock number: 018158
Research areas: Cancer Research, Research Tools

Description

These Trask knockout mice carry a deletion mutation of the Cdcp1 gene, and may be useful in studies of integrin signaling, anoikis resistance, cell adhesion and tumor metastasis.

Detailed description

CUB domain-containing protein 1, Cdcp1, is a substrate of Src family kinases and is involved in anoikis resistance and cell adhesion, as well as cancer progression and tumor metastasis. These mice carry a knockout mutation of the Cdcp1 gene, in which exon 1 has been deleted. Mice that are homozygous for the mutation are viable and fertile. No gene product (protein) is detected by Western blot analysis of skin and intestine from homozygous mice.

When bred to MMTV-PyMT mice, the resulting double mutant mice exhibit accelerated development of mammary tumors.

Development

A targeting vector containing a FRT site-flanked NEO cassette was utilized in the construction of this mutant. A loxP site and the selection cassette were inserted downstream of exon 1 of the targeted gene, and another loxP site was inserted upstream of exon 1. This construct was electroporated into unspecified 129/SvJ derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric male animals were backcrossed to female mice expressing FLP1 recombinase under the control of an actin promoter (on the C57BL/6 background) to remove the FRT-flanked NEO cassette. The mice were then crossed to mice (on the C57BL/6 genetic background) expressing Cre recombinase under the control of the adenovirus EIIa promoter to excise exon 1. The mice were then crossed to C57BL/6 for six generations (see SNP results below) prior to sending males to The Jackson Laboratory Repository in 2012. Upon arrival, males were bred to C57BL/6J females (Stock No. 000664) at least once to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the first generation rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Allele

Symbol: Cdcp1^tm1.2Moas
Name: targeted mutation 1.2, Mark Moasser
MGI accession ID: MGI:5442763
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Cdcp1
Marker name: CUB domain containing protein 1
Marker synonyms: 9030022E12Rik; CD318; E030027H19Rik; RGD1305578; SIMA135; TRASK
Chromosome: 9
Strain of origin: 129
Molecular note: A targeting vector containing a FRT site-flanked NEO cassette was utilized in the construction of this mutant. A loxP site and the selection cassette were inserted downstream of exon 1 of the targeted gene, and another loxP site was inserted upstream of exon 1. Flp-mediated recombination removed the neo cassette and cre-mediated recombination removed exon 1. No gene product (protein) is detected by Western blot analysis of skin and intestine from homozygous mice.