B6;129P2-Siva1^{Gt(RRR467)Byg}/AttJ

Stock number: 034349
Product name: Siva⁻
Research areas: Apoptosis Research, Cell Biology Research, Research Tools

Description

Siva^- mice have a gene trap vector, containing engrailed 2 (En2) intronic sequences followed by a splice acceptor (SA) and coding sequences for the β-galactosidase-neomycin (β-geo) gene followed by an SV40 polyadenylation sequence inserted into exon 1 of the SIVA1, apoptosis-inducing factor (Siva1) gene. This strain may be useful for studying the pro-apoptotic roles of SIVA1, and its potential as a cancer therapy target.

Detailed description

Siva^- mice carry a gene trap vector containing engrailed 2 (En2) intronic sequences followed by a splice acceptor (SA) and coding sequences for the β-galactosidase-neomycin (β-geo) gene followed by an SV40 polyadenylation sequence inserted into exon 1 of the Siva1 gene, which encodes the apoptosis-inducing factor Siva1. SIVA1 is direct target of the p53 tumor suppressor but can also act in a p53-independent manner. SIVA1 is necessary for efficient oncogenic KRAS–driven non–small cell lung cancer (NSCLC) development. Loss of Siva inhibits tumor formation making it a potential cancer therapy target. In this gene-trapped model, SIVA1 deficiency causes early embryonic lethality accompanied by multiple developmental phenotypes, including developmental delay, abnormal neural tube closure, and defective placenta and yolk sac formation. LacZ expression is seen in embryonic and extra-embryonic tissues such as the primitive streak, allantois, and yolk sac at E7.5. Between E8.5 and E11.5 SIVA1 expression is obvious in the allantois and umbilical cord as well as in the heart and forebrain. Heterozygous mice are viable and fertile while homozygous mice are embryonic lethal between e8.5 and e12.5.

Development

A gene trap vector (pGT0Lxf) containing engrailed 2 (En2) intronic sequences followed by a splice acceptor (SA) and coding sequences for the β-galactosidase-neomycin (β-geo) gene and an SV40 polyadenylation sequence was electroporated into 129P2/OlaHsd-derived embryonic stem (ES) cells. An ES cell line (RR467) in which the gene-trap vector was inserted into exon 1 of the SIVA1, apoptosis-inducing factor (Siva1) gene was identified by 5′ rapid amplification of cDNA ends (RACE) followed by automated DNA sequencing. Siva1-targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred with C57BL/6J mice (Stock No. 000664). Siva^- offspring were maintained on a mixed genetic background. Upon arrival at The Jackson Laboratory, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes.

Allele

Symbol: Siva1^{Gt(RRR467)Byg}
Name: gene trap RRR467, BayGenomics
MGI accession ID: MGI:4330573
Generation method: Gene trapped
Marker symbol: Siva1
Marker name: SIVA1, apoptosis-inducing factor
Marker synonyms: CD27bp; Siva; Siva-1; Siva-2
Chromosome: 12
Strain of origin: 129P2/OlaHsd
Molecular note: Trapped gene association determined by genome coordinate overlap and strand. The gene trap vector is inserted near the 5'-end of exon 1.