A nonactivating <i>ITGB3</i> mutation in the β3 cytoplasmic region causes macrothrombocytopenia with an impaired αIIbβ3/RhoA pathway.

ABSTRACT: Almost all mutations of ITGA2B or ITGB3 identified in congenital macrothrombocytopenia induce constitutive activation of αIIbβ3. However, whether concomitant αIIbβ3 activation is essential for macrothrombocytopenia development remains unknown. Recently, we identified the β3(R760C) mutation that does not induce αIIbβ3 activation in a patient with macrothrombocytopenia. The family study showed that macrothrombocytopenia with reduced expression of αIIbβ3 and glycoprotein IV (GPVI) appeared to be associated with patients heterozygous for β3(R760C). We generated β3(R760C) knockin (KI) mice and investigated the effects of the mutation on platelet/megakaryote biology. Macrothrombocytopenia was decreased to 76% and 40% of platelet counts in heterozygous (Hetero) and homozygous (Homo)

SUBMITTER: Nakata K 

PROVIDER: S-EPMC12320448 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature