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Blood, 1 May 2004, Vol. 103, No. 9, pp. 3396-3402.
Prepublished online as a Blood First Edition Paper on January 22, 2004; DOI 10.1182/blood-2003-10-3721.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Genetic variation responsible for mouse strain differences in integrin 2 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, and
Paul F. Bray
From the Departments of Medicine and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX; the Lawrence Berkeley Laboratories, Berkeley, CA; and the Department of Vascular Biology, Rudolf Virchow Center for Experimental Biomedicine Versbacher, Würzburg, Germany.
As mouse models have become commonplace 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 IIb, integrin 3, glycoprotein (GP) Ib , or GPVI across strains. However, FVB platelets expressed approximately 50% the level of integrin 2 as platelets from other strains (P < .0001). We bred FVB mice with C57 and assessed 2 expression in FVB/C57xFVB/C57 (F2) offspring. Linkage analysis demonstrated the gene responsible for 2 levels is tightly linked to the D13mit260 marker (log odds [lod] score 6.7) near the 2 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 PLC 2 tyrosine phosphorylation. Thus, FVB platelets express half the level of 2 as other mouse strains, a trait linked to the 2 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 2 1 expression and demonstrate that 2 1 participates in signaling during platelet activation. (Blood. 2004;103:3396-3402)

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