Mice Expressing Low Levels of CalDAG-GEFI Exhibit Markedly Impaired Platelet Activation With Minor Impact on Hemostasis.

ABSTRACT:

Objective

The tight regulation of platelet adhesiveness, mediated by the αIIbβ3 integrin, is critical for hemostasis and prevention of thrombosis. We recently demonstrated that integrin affinity in platelets is controlled by the guanine nucleotide exchange factor, CalDAG-GEFI (CD-GEFI), and its target, RAP1. In this study, we investigated whether low-level expression of CD-GEFI leads to protection from thrombosis without pathological bleeding in mice.

Approach and results

Cdg1(low) mice were generated by knockin of human CD-GEFI cDNA into the mouse Cdg1 locus. CD-GEFI expression in platelets from Cdg1(low) mice was reduced by ≈90% when compared with controls. Activation of RAP1 and αIIbβ3 was abolished at low agonist concentrations and partially inhibited at high agonist con

SUBMITTER: Piatt R 

PROVIDER: S-EPMC5001889 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature