title: The function of ADAMTS13 in thrombogenesis in vivo: insights from mutant mice.
abstract: 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.
authors.affiliation: National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka, 565-8565, Japan. banno@ri.ncvc.go.jp
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Banno
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chauhan
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
mesh_terms: 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
chemical_list: D014841:von Willebrand Factor; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein