The third exon of the mouse Sav1 gene was flanked by loxP sites to create this Sav1flox strain. Cre-mediated excision of the floxed region disrupts transcription of the gene and creates a knockout allele.
Duojia Pan, Johns Hopkins University School of Medicine
Sav1 (salvador homolog 1 (Drosophila)) encodes a tumor suppressor that normally restricts Yap1 (yes-associated protein 1;) oncogene activity.
The third exon of the mouse Sav1 gene was flanked by loxP sites to create this Sav1flox strain. Cre-mediated excision of the floxed region disrupts transcription of the gene and creates a knockout allele. Mice homozygous for a Sav1 knockout are perinatal lethal. A small portion of mutant mice are born but die very soon after birth.
Progeny of Sav1flox animals crossed with Vil-Cre mice (see Stock No. 004586) show an enlargement of crypts in both the colon and small intestine, which contain more and faster proliferating cells. The hyperplasia in the crypts is completely reversed by loss of YAP1 (see Stock No. 027929 for a floxed conditional strain), even though the latter by itself has no visible effect on normal crypt morphology or cell proliferation. By 13 months of age, all male compound mutant mice develop colonic polyps, whereas none are found in control mice.
A loxP site was introduced to intron 2 and an FRT-neomycin-FRT-loxP cassette was placed in intron 3 via homologous recombination in 129P2/OlaHsd-derived E14TG2a.4 embryonic stem (ES) cells. Resultant mice were crossed with CMV-FLP recombinase-expressing animals on a C57BL/6 background to excise the neomycin cassette, leaving exon 3 flanked by loxP sites. This strain was maintained on a mixed C57BL/6-129 genetic background by the donating lab.
|Allele Name||targeted mutation 1.1, Duojia Pan|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Sav1, salvador family WW domain containing 1|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A loxP site was inserted upstream of exon 3 and an FRT flanked neo cassette with a 3' loxP site was inserted downstream of exon 3. Flp mediated recombination removed the neo cassette leaving exon 3 floxed.|
Homozygous and heterozygous floxed mice are viable and fertile.
When using the Sav1flox mouse strain in a publication, please cite the originating article(s) and include JAX stock #027933 in your Materials and Methods section.