International Journal of Hematology

, Volume 91, Issue 1, pp 30–35

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

  • Fumiaki Banno
  • Anil K. Chauhan
  • Toshiyuki Miyata
Progress in Hematology Recent advance in thrombotic thrombocytopenic purpura

DOI: 10.1007/s12185-009-0477-0

Cite this article as:
Banno, F., Chauhan, A.K. & Miyata, T. Int J Hematol (2010) 91: 30. doi:10.1007/s12185-009-0477-0

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.

Keywords

ADAMTS13von Willebrand factorADAMTS13-deficient miceADAMTS13-congenic miceThrombosisInflammation

Copyright information

© The Japanese Society of Hematology 2010

Authors and Affiliations

  • Fumiaki Banno
    • 1
  • Anil K. Chauhan
    • 2
  • Toshiyuki Miyata
    • 1
  1. 1.National Cardiovascular Center Research InstituteSuitaJapan
  2. 2.Department of Internal MedicineUniversity of Iowa Carver College of MedicineIowaUSA