Exons 11-15 protein S (alpha) (Pros1) gene are flanked by loxP sites in these Pros1fl/fl mutant. This strain may be useful for studying clotting, coagulation, and vascular development and homeostasis.
Greg Lemke, The Salk Institute
Exons 11-15 protein S (alpha) (Pros1) gene are flanked by loxP sites. The frt-flanked neo is still present in this strain, and the donating investigator reports no change in phenotype due to the neo cassette. PROS1 is a vitamin K-dependent blood anticoagulant expressed in the endothelium. It functions in the removal of apoptotic cells from circulation and degradation of factors Va and VIIIa. It has also been implicated in vascular development and homeostasis. Deficiencies have been associated with venous thrombosis, stroke, and autoimmunity. Mice that are homozygous for this floxed allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 11-15 deleted in cre-expressing tissues.
When bred to B6.FVB-Tg(EIIa-cre)C5379Lmgd/J mice (Stock No. 003724) expressing cre in the developing embryo, homozygous offspring die in utero between E15.5 and E17.5 from massive coagulopathy and hemorrhaging, while heterozygous offspring are viable but infertile.
When bred to B6.Cg-Tg(Alb-cre)21Mgn/J mice (Stock No. 003574) expressing Cre recombinase in hepatocytes, blood vessels of offspring contained some fibrin-containing clots but overall displayed less-severe coagulopathy than that seen in the complete Pros1 knockout.
When bred to B6.Cg-Tg(Tagln-cre)1Her/J mice (Stock No. 017491) expressing Cre recombinase in smooth muscle, offspring exhibits leaky vasculature in the liver.
A targeting vector was designed to insert a loxP site upstream of exon 11, and a frt-flanked neomycin resistance cassette and another loxP site downstream of exon 15 of the protein S (alpha) (Pros1) gene. The construct was electroporated into 129S1/SvImJ-derived 2A embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females (see SNP note below). Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.
A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Twenty of the 27 markers throughout the genome were segregating, suggesting a mixed genetic background.
|Allele Name||targeted mutation 1, Greg Lemke|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Allele Synonym(s)||ProSfl; Pros1fl|
|Gene Symbol and Name||Pros1, protein S (alpha)|
|Strain of Origin||129S1/SvImJ|
|Molecular Note||A loxP site was inserted upstream of exon 11. An FRT-flanked neomycin resistance cassette with a 5' loxP site was inserted downstream of exon 15.|
When maintaining a live colony mice homozygous for the floxed allele may be bred together.
When using the STOCK Pros1tm1Grl/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022972 in your Materials and Methods section.
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