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.
