As mouse models have become common-place for studying hemostasis and thrombosis, we considered whether the mouse system had utility for assessing genetic alterations in platelet receptors. Platelets from 5 mouse strains (C57BL/6 [C57], FVB/N [FVB], BALB/c, C3H/He, and 129Sv) showed only minor differences in the expression of integrin αIIb, integrin β3, glycoprotein (GP) Ibα, or GPVI across strains. However, FVB platelets expressed approximately 50% the level of integrin α2 as platelets from other strains (P < .0001). We bred FVB mice with C57 and assessed α2 expression in FVB/C57xFVB/C57 (F2) offspring. Linkage analysis demonstrated the gene responsible for α2 levels is tightly linked to the D13mit260 marker (log odds [lod] score 6.7) near the α2 gene. FVB platelets showed reduced aggregation and a longer lag phase to collagen. FVB and C57 platelets aggregated similarly to collagen-related peptide, but FVB platelets showed a reduction in rhodocytin-induced Syk and PLCγ2 tyrosine phosphorylation. Thus, FVB platelets express half the level of α2 as other mouse strains, a trait linked to the α2 gene and seemingly responsible for reduced platelet aggregation to collagen. These strain differences serve as a useful model for the 2-fold difference in human platelet α 2β1 expression and demonstrate that α 2β1 participates in signaling during platelet activation.
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