|June 26, 2012|
New Humanized Mouse Model for Developing Hemophilia A Therapy
We are now accepting orders for STOCK F8tm1Kaz Tg(Alb-F8*R593C)T4Mcal/J (017706), a mouse model that may be used to develop Factor VIII (F8) treatments for human hemophilia A, an inherited bleeding disorder that primarily affects males.
F8 is a coagulation factor whose mutations are prevalent in patients with hemophilia A. The new "humanized F8" double mutant is deficient for endogenous mouse F8 and transgenic for a mutant form of human F8 (hF8) that is commonly found in patients with hemophilia A. The transgene is driven by the mouse albumin (Alb) promoter and contains an arginine-to-cysteine missense mutation at amino acid 593 within the human F8 gene.
Unlike the F8 knockout model, B6;129S4-F8tm1Kaz/J (004424), the humanized F8 model tolerates injections of normal hF8, produces very few inhibitory anti-F8 antibodies, and lacks hF8 responsive T or B cells.
Because they lack the F8 coagulation factor, both the F8 and the humanized F8 models should not be tail-clipped until they are four weeks old. Their wounds should be cauterized to prevent death due to blood loss.
The humanized F8 model may be used to develop targeted therapies for hemophilia A. When treated with a plasmid that expresses normal hF8 driven by a liver-specific human α1 anti-trypsin promoter and an attB phiC31 integrase site (along with a phiC31 integrase treatment), the normal hF8 integrates into the genome at specific "pseudo-attP sites" and conveys long-term gene therapy (Bril et al. 2006).
You can order this model via the strain data sheet.