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.
Banno
Fumiaki
F
National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. banno@ri.ncvc.go.jp
Chauhan
Anil K
AK
Miyata
Toshiyuki
T
D000071120:ADAMTS13 Protein; D000818:Animals; D004195:Disease Models, Animal; D008666:Metalloendopeptidases / Q000097:blood* / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D010974:Platelet Aggregation / Q000502:physiology; D013927:Thrombosis / Q000097:blood* / Q000235:genetics*; D014841:von Willebrand Factor / Q000378:metabolism
D014841:von Willebrand Factor; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein