These mice carry the F5 Leiden mutation whereby the arginine at position 504 is replaced by a glutamine disrupting a cleavage site necessary for the inactivation of the factor V protein. Mice that are homozygous for this allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Clotting activity is indistinguishable from that of wildtype mice. Rarely, spontaneous vascular thrombo-embolic events are observed. Analysis of tissue fibrin content indicates increased deposition of fibrin in multiple tissues. When maintained on a mixed B6;129 genetic background, mice homozygous for this allele experience disseminated intravascular thrombosis resulting in increased fetal loss. This loss is not observed on a congenic C57BL/6J genetic background. This mutant mouse strain represents a model useful in research examining the disease aspects of the Leiden mutation and thrombosis in general.
A targeting vector containing F5 exons 7-11, with a TK/neo cassette flanked by loxP sites located in intron 10 and a point mutation in exon 10 (mutation R504Q) was introduced into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with supercoiled pMC-Cre plasmid DNA to remove the TK/neo cassette. ES cells bearing the R504Q mutation and bereft of the TK/Neo cassette were injected into C57BL/6J blastocysts. The resulting chimeric male animals were backcrossed to C57BL/6J females. Mutant mice were then backcrossed to C57BL/6J for twelve generations before being made homozygous.
|Allele Name||targeted mutation 2, David Ginsburg|
|Allele Type||Targeted (Hypomorph, Humanized sequence)|
|Allele Synonym(s)||targeted mutation 2, David Ginsburg; F5tm2Dgi|
|Gene Symbol and Name||F5, coagulation factor V|
|Gene Synonym(s)||Cf5; RPRGL1; Cf-5; Cf5; expressed sequence AI173222; THPH2; AI173222; PCCF; Ac2-120; FVL; Cf-5|
|Promoter||F5, coagulation factor V, mouse, laboratory|
|Strain of Origin||129S2/SvPas|
|Molecular Note||A point mutation was introduced which altered the codon corresponding to amino acid 504 from an arginine to a glutamine (R504Q). A loxP flanked neomycin cassette in intron 10 was removed by Cre-mediated recombination in ES cells prior to blastocyst injection.|
|Mutations Made By|| |
Jisong Cui, University of Michigan
This strain originated on a B6;129P background and has been backcrossed to C57BL/6J for twelve generations before being made homozygous.
When using the B6.129S2-F5tm2Dgi/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004080 in your Materials and Methods section.
|Heterozygous or wildtype for F5<tm2Dgi>|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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