| First Author | Banno F | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 21 | Pages | 5323-9 |
| PubMed ID | 19109562 | Mgi Jnum | J:148975 |
| Mgi Id | MGI:3847200 | Doi | 10.1182/blood-2008-07-169359 |
| Citation | Banno F, et al. (2009) The distal carboxyl-terminal domains of ADAMTS13 are required for regulation of in vivo thrombus formation. Blood 113(21):5323-9 |
| abstractText | ADAMTS13 is a multidomain protease that limits platelet thrombogenesis through the cleavage of von Willebrand factor (VWF). We previously identified 2 types of mouse Adamts13 gene: the 129/Sv-strain Adamts13 gene encodes the long-form ADAMTS13 having the same domains as human ADAMTS13, whereas the C57BL/6-strain Adamts13 gene encodes the short-form ADAMTS13 lacking the distal C-terminal domains. To assess the physiologic significance of the distal C-terminal domains of ADAMTS13, we generated and analyzed 129/Sv-genetic background congenic mice (Adamts13(S/S)) that carry the short-form ADAMTS13. Similar to wild-type 129/Sv mice (Adamts13(L/L)), Adamts13(S/S) did not have ultralarge VWF multimers in plasma, in contrast to 129/Sv-genetic background ADAMTS13-deficient mice (Adamts13(-/-)). However, in vitro thrombogenesis under flow at a shear rate of 5000 s(-1) was accelerated in Adamts13(S/S) compared with Adamts13(L/L). Both in vivo thrombus formation in ferric chloride-injured arterioles and thrombocytopenia induced by collagen plus epinephrine challenge were more dramatic in Adamts13(S/S) than in Adamts13(L/L) but less than in Adamts13(-/-). These results suggested that the C-terminally truncated ADAMTS13 exhibited decreased activity in the cleavage of VWF under high shear rate. Role of the C-terminal domains may become increasingly important under prothrombotic conditions. |
