Genetic variation responsible for mouse strain differences in integrin α₂ expression is associated with altered platelet responses to collagen

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 α_IIb, 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.