STOCK Krt19^{tm1(cre/ERT)Ggu}/J

Stock number: 026925
Product name: K19^CreERT
Research areas: Research Tools

Description

This strain is currently unavailable due to replenishing of cryopreserved stocks. Interested customers who register interest will be contacted when the strain is again available.

 

K19^CreERT knock-in/knock-out mice may be useful for applications requiring tamoxifen-induced deletion of floxed sequences in KRT19-expressing epithelial cells.

Detailed description

K19^CreERT mice have a cre^ERT fusion gene (a Cre recombinase fused to a mouse estrogen receptor ligand binding domain) inserted upstream of the initiation codon of the keratin 19 (Krt19) gene. The presence of cre^ERT and a 3' polyadenylation signal abolishes expression of KRT19. K19 is an intermediate filament protein expressed in multiple epithelial cell types from the epiblast stage though adult. Specifically, expression is seen in lung, oral cavity, bronchi, bronchioles, stomach, small intestines, and in the pancreatic, renal, and hepatic ductal cells.

Restricted to the cytoplasm, cre^ERT can only gain access to the nuclear compartment after exposure to tamoxifen.

When these K19^CreERT mice are bred with those containing loxP-flanked sequences, tamoxifen-inducible, Cre-mediated recombination will result in deletion of the floxed sequences in the Cre-expressing cells of the offspring. Publications indicate intraperitoneal injections of tamoxifen may be favorable compared to other methods (e.g., administration via oral gavage).

In the absence of tamoxifen, leaky cre activity is detected in less than 1% of stomach and intestinal epithelial cells, but not in pancreatic or hepatic epithelial tissues. Homozygous mice are viable and fertile.

Development

A targeting construct was designed to insert a cre^ERT fusion gene (a Cre recombinase fused to a mouse estrogen receptor ligand binding domain) followed by a frt-flanked neomycin resistance (neo) cassette and a polyadenylation signal upstream of the transcription initiation codon of the keratin 19 (Krt19) gene. This construct was electroporated into 129S6/SvEvTac-derived TL1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and the resulting chimeric mice were bred to Tg(ACTFLPe)9205Dym/J transgenic mice to remove the neo cassette. K19^CreERT offspring were bred together to remove the flp-expressing transgene, and their progeny were bred to ICR mice. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Krt19^{tm1(cre/ERT)Ggu}
Name: targeted mutation 1, Guoqiang Gu
MGI accession ID: MGI:3797107
Generation method: Targeted
Attributes: Recombinase-expressing; Inducible
Marker symbol: Krt19
Marker name: keratin 19
Chromosome: 11
Strain of origin: 129S6/SvEvTac
Expressed genes: cre/ERT2,Cre recombinase and estrogen receptor 1 (human) fusion gene,
Site of expression: Cre expression is restricted to epithelial cells in multiple endodermal organs.
Molecular note: An inducible cre/ESR1 fusion gene followed by an frt-flanked neo cassette was inserted upstream of the translation initiation codon. Cre expression is restricted to epithelial cells in multiple endodermal organs (pancreatic ducts, hepatic ducts, stomach and intestine).