F8F floxed mice may be useful for conditional deletion of coagulation factor VIII in studies of hemophilia A.
Robert R Montgomery, Blood Research Institute / BloodCenter of Wisconsin
F8F floxed mice possess loxP sites flanking exons 17-18 of the X-linked coagulation factor VIII (F8) gene. F8 is a blood coagulation factor primarily expressed in liver. Defects in F8 are associated with hemophilia A, a common recessive X-linked coagulation disorder. Homozygous females and hemizygous males are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exons 17-18 deleted in the cre-expressing tissues.
For example, when bred to B6.Cg-Tg(Alb-cre)21Mgn/J mice (Stock No. 003574) expressing cre in hepatocytes, resulting mice had FVIII levels and phenotype similar to floxed littermates.
When bred to B6.Cg-Tg(Tek-cre)1Ywa/J mice (Stock No. 008863) expressing cre in endothelial cell, resulting offspring display a severe hemophilic phenotype with no
detectable plasma FVIII activity, similar to F8 KO mice.
A targeting vector was designed to insert a loxP site upstream of exon 17, and a frt-flanked neomycin resistance (neo) cassette followed by a second loxP site downstream of exon 18 of the X-linked coagulation factor VIII (F8) gene. The construct was electroporated into 129 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 with B6.Cg-Tg(ACTFLPe)9205Dym/J transgenic mice (Stock No. 005703) to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. Resulting F8F mice were maintained on a mixed 129S;B6 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, Robert Montgomery|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||F8, coagulation factor VIII|
|Strain of Origin||129|
|Molecular Note||Exons 17 and 18 and FRT-flanked neo cassette were flanked by two loxP sites. FLP-mediated recombinase removed the neo cassette, leaving exons 17 and 18 floxed.|
When maintaining a live colony, homozygous females and hemizygous males may be bred together.
When using the STOCK F8tm1.1Rmnt/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #026199 in your Materials and Methods section.