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Shigatoxin triggers thrombotic thrombocytopenic purpura in genetically susceptible ADAMTS13-deficient mice.

Authors: Motto, DG  Chauhan, AK  Zhu, G  Homeister, J  Lamb, CB  Desch, KC  Zhang, W  Tsai, HM  Wagner, DD  Ginsburg, D 
Citation: Motto DG, etal., J Clin Invest. 2005 Oct;115(10):2752-61.
Pubmed: (View Article at PubMed) PMID:16200209
DOI: Full-text: DOI:10.1172/JCI26007

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening illness caused by deficiency of the vWF-cleaving protease ADAMTS13. Here we show that ADAMTS13-deficient mice are viable and exhibit normal survival, although vWF-mediated platelet-endothelial interactions are significantly prolonged. Introduction of the genetic background CASA/Rk (a mouse strain with elevated plasma vWF) resulted in the appearance of spontaneous thrombocytopenia in a subset of ADAMTS13-deficient mice and significantly decreased survival. Challenge of these mice with shigatoxin (derived from bacterial pathogens associated with the related human disease hemolytic uremic syndrome) resulted in a striking syndrome closely resembling human TTP. Surprisingly, no correlation was observed between plasma vWF level and severity of TTP, implying the existence of TTP-modifying genes distinct from vWF. These data suggest that microbe-derived toxins (or possibly other sources of endothelial injury), together with additional genetic susceptibility factors, are required to trigger TTP in the setting of ADAMTS13 deficiency.

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CRRD Object Information
CRRD ID: 10449037
Created: 2015-12-15
Species: All species
Last Modified: 2015-12-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.