Mice that are homozygous for the targeted, X chromosome-linked mutant allele are viable and fertile. Homozygous females and carrier males have less than 1% of normal factor VIII activity and exhibit prolonged clotting times. Care should be used when obtaining tail clippings for the purpose of genotyping. Clipped tails of affected mice must be cauterized immediately or the mouse will succumb to excessive blood loss within several hours. Only mice that have reached the age of 4 weeks or older should have their tails clipped. Published reports indicate that spontaneous bleeding into joints or soft tissues, and that no bleeding difficulties are apparent during birth. These mice recapitulate key features of hemophilia A and provide an excellent model for use in exploring gene therapy strategies.
NOTE: It has been the experience of The Jackson Laboratory, in contrast to the primary publication, and possibly due to genetic background differences as a result of continuous inbreeding, animals homozygous or hemizygous for the F8tm1Kaz allele do exhibit bleeding into joints and soft tissues.
A targeting vector containing a neo cassette was used to disrupt exon 16. The construct was introduced into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Haig H Kazazian Jr|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||E-16; FVIII KO; HemA; MFVIII-16|
|Gene Symbol and Name||F8, coagulation factor VIII|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A neomycin resistance cassette replaced 293 bp of sequence, including 7 bp at the 3' end of exon 16 and 286 bp at the 5' end of intron 16. Two different activity assays indicated that the mutated allele produced protein with levels of activity less than 1% of wild-type levels.|
|Mutations Made By|| |
Haig Kazazian, Jr., University of Pennsylvania
This strain originated on a B6;129S4 background. It is maintained by crossing homozygous females x hemizygous males on the same background. Expected coat color: Agouti and black. Homozygous females and carrier males have less than 1% of normal factor VIII activity and exhibit prolonged clotting times. Care should be exercise when obtaining tail clippings for genotyping purposes. Clipped tails of affected mice must be cauterized immediately, or the mouse will succumb to excessive blood loss within several hours. Preparing genomic DNA from ear punches is recommended.
NOTE: It has been the experience of The Jackson Laboratory, in contrast to the primary publication and possibly due to genetic background differences as a result of continuous inbreeding, that animals homozygous or hemizygous for the F8tm1Kaz allele do exhibit bleeding into joints and soft tissues.
When using the B6;129S-F8tm1Kaz/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #004424 in your Materials and Methods section.
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