Plasma removal of human FVIII in MX1cre⁺LRP^flox/flox and control LRP^flox/flox mice.

MX1cre⁺LRP^flox/flox mice () (n = 6) and control LRP^flox/flox mice (○) (n = 6) were injected 3 times intraperitoneally with pI:pC at 2-day intervals. At 10 days after the final injection, endogenous mouse plasma FVIII levels were 1.7 U/mL (range, 1.5-1.9 U/mL) and 3.3 U/mL (range, 2.8-3.8 U/mL) for control LRP^flox/flox and MX1cre⁺LRP^flox/flox mice, respectively. Endogenous plasma VWF levels were 1.1 U/mL (range, 1.0-1.3 U/mL) and 1.3 U/mL (range, 1.2-1.4 U/mL), for control LRP^flox/floxand MX1cre⁺LRP^flox/flox mice, respectively. Then, purified human FVIII (20 IU) was administered intravenously. Plasma removal was monitored at 1, 30, 60, 120, 180, 300, and 420 minutes after injections, and FVIII levels were determined. Data represent geometric mean values and 68% confidence intervals, and are expressed as a percentage of the amount of FVIII present in thet = 1 minute plasma sample. The curves were analyzed by means of double-exponential fits. *P < .02 and **P < .001, significantly different from control LRP^flox/flox mice, with the use of the Mann-WhitneyU test. Inset shows detection of LRP in the liver membrane extracts of control LRP^flox/flox mice (n = 2) (lanes 1-2), and MX1cre⁺LRP^flox/flox mice (n = 2) (lanes 3-4). Immunoblotting experiments were performed as described in “Materials and methods.”