Sivafl mice have loxP sites flanking exons 1-4 of the SIVA1, apoptosis-inducing factor (Siva1) gene. This strain may be useful for studying the pro-apoptotic roles of Siva, and its potential as a cancer therapy target.
Laura Attardi, Stanford University Medical Center
Sivafl mice have loxP sites flanking exons 1-4 of the SIVA1, apoptosis-inducing factor (Siva1) gene. Siva is a pro-apoptotic protein through its ability to induce CD27-mediated apoptosis. It is also a direct target for p53, a critical tumor suppressor. Siva has also been shown to play a role in promoting proliferation and tumorigenesis in a p53-independent manner by stimulating mTOR signaling and metabolism. 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 exons 1-4 deleted in cre-expressing tissues. If Siva is deleted in the whole-body during development, mice are embryonic lethal.
For example, when crossed to B6.129S4-Krastm4Tyj/J mice (Stock No. 008179), which have an upstream floxed transcriptional stop cassette blocking expression of an oncogenic KrasG12D protein, and compound mutant mice are infected with Ad-Cre to drive expression of KrasG12D and excision of the Siva locus in the lung, resulting mice have fewer adenomas and adenocarcinomas, and reduced tumor burden. In this model, Siva inactivation inhibits non–small cell lung cancer (NSCLC) development.
A targeting vector was designed to insert a single loxP upstream of exon 1, and a loxP-flanked puromycin resistance (puro) cassette site downstream of exon 4 of the SIVA1, apoptosis-inducing factor (Siva1) gene. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric males were bred with C57BL/6J females. Offspring were bred to CMV-cre mice on a 129Sv;C57BL/6J background to delete the puro cassette. Resulting mice contained multiple gene rearrangments; intact floxed-exons 1-4, intact floxed-puro cassette, or excision of exons 1-4 and the puro cassette. Progeny containing only the floxed-exons 1-4 were bred with 129Sv;C57BL/6J mice and the resulting colony of Sivafl mice were maintained on a mixed background. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
|Allele Name||targeted mutation 1.1, Laura D Attardi|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Siva1, SIVA1, apoptosis-inducing factor|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A targeting vector is designed to insert a single loxP upstream of exon 1, and a loxP-flanked puromycin resistance (puro) cassette site downstream of exon 4 of the SIVA1, apoptosis-inducing factor (Siva1) gene. Cre-mediated recombination removed the floxed puro cassette leaving exons 1-4 floxed.|
When maintaining a live colony mice homozygous for the floxed allele may be bred together.
When using the Sivafl mouse strain in a publication, please cite the originating article(s) and include JAX stock #027800 in your Materials and Methods section.