The function of ADAMTS13 in thrombogenesis in vivo: insights from mutant mice.

Recently, two independent groups have established ADAMTS13-deficient mice using gene-targeting techniques. In humans, genetic or acquired deficiency in ADAMTS13 leads to a potentially fatal syndrome, thrombotic thrombocytopenic purpura (TTP). Surprisingly, ADAMTS13-deficient mice are viable with no apparent signs of TTP. However, these mouse models indicate that ADAMTS13 down-regulates platelet adhesion and aggregation in vivo, and ADAMTS13 deficiency can provide enhanced thrombus formation at the site of vascular lesions. In addition, ADAMTS13 by cleaving hyperactive ultra-large von Willebrand factor multimers not only down-regulates thrombosis but also inflammation. ADAMTS13-congenic mice that carry a truncated form of ADAMTS13 lacking the C-terminal domains have also been developed. Phenotypes of the congenic mice indicate the physiological significance of the C-terminal domains of ADAMTS13 in down-regulating thrombus growth. The studies mentioned here in different mouse models uncover the in vivo function of ADAMTS13 and strengthened the understanding of the mechanism of systemic disease TTP.