B6J.129S-Crk^tm1.1Imo/J

Stock number: 032874
Product name: Crk ^f/+ or Crk ^f/f, Crk Flox
Research areas: Cardiovascular Research, Developmental Biology Research, Research Tools

Description

Crk^f has loxP sites flanking exon 1. Exposure to Cre recombinase will delete exon 1 and result in the knock-out allele. These mice may be useful in studying DiGeorge syndrome and tumorigenesis.

Detailed description

The targeted Crk oncogene encodes an adapter protein with similarities to its paralog, Crkl, such as src-homology domains SH2 and SH3, expression pattern, and involvement in signal transduction. Up-regulation of the Crk gene has been associated with several types of human cancer. These mice possess loxP sites on either side of exon 1 of the targeted gene. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues.
Removal of the floxed sequence creates a null allele.

Development

A targeting vector containing an FRT site flanked PGKneo selection cassette with a downstream loxP site was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 1 of the targeted gene, and another loxP site was inserted upstream of exon 1. This construct was electroporated into 129S6-derived PRX129 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were bred to C57BL/6J to achieve germline transmission. The mice were crossed to B6.129S4-Gt(ROSA)26Sor^tm1(FLP1)Dym/J (Stock No. 009086) mice to remove the FRT site flanked PGKneo cassette. The mice were then crossed to C57BL/6 to breed out the FLP recombinase allele, and backcrossed to C57BL/6J for 11 generations. During backcrossing, the Y chromosome was fixed to the C57BL/6J genetic background. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Crk^tm1.1Imo
Name: targeted mutation 1.1, Akira Imamoto
MGI accession ID: MGI:6275121
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Crk^f
Marker symbol: Crk
Marker name: v-crk avian sarcoma virus CT10 oncogene homolog
Marker synonyms: Crk-I; CrkII; Crk-II; Crk-III; Crko; p38; proto-oncogene c-crk
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Molecular note: The targeting vector contains an FRT site flanked PGKneo selection cassette with a downstream loxP site. This selection cassette was inserted downstream of exon 1 of the targeted gene, and another loxP site was inserted upstream of exon 1. FLP-mediated recombination removed the FRT-flanked neo cassette leaving exon 1 floxed.