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

Tong Tong Li, Susana Larrucea, Shiloe Souza, Suzanne M. Leal, José A. López, Edward M. Rubin, Bernhard Nieswandt, Paul F. Bray

    Research output: Contribution to journalArticlepeer-review

    39 Scopus citations

    Abstract

    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.

    Original languageEnglish (US)
    Pages (from-to)3396-3402
    Number of pages7
    JournalBlood
    Volume103
    Issue number9
    DOIs
    StatePublished - May 1 2004

    ASJC Scopus subject areas

    • Biochemistry
    • Immunology
    • Hematology
    • Cell Biology

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