The beige (bgJ/bgJ) mouse is a well-described murine model of
Chediak-Higashi syndrome. Platelet function was examined in normal and beige mice to better characterize the defective aggregation response in platelets from mice with
Chediak-Higashi syndrome. Platelet aggregation after
collagen,
thrombin, and
phorbol-12-myristate 13-acetate stimulation was significantly (P less than 0.025) decreased in platelets from beige mice, relative to platelets from normal mice. Compared with beige and normal mice, those heterozygous for the bg trait had intermediate responses to
collagen and
thrombin, but not
phorbol-12-myristate 13-acetate. The defect(s) in aggregation of platelets from beige mice was associated with a dense granule
storage pool deficiency and decreased stores of
serotonin and
adenine nucleotides in platelets. Mice heterozygous for the bg trait had normal platelet
serotonin and
adenine nucleotide concentrations. Platelets from beige mice were approximately 10 times more sensitive to
prostacyclin inhibition of
collagen-induced aggregation than were platelets from control mice. However, a significant difference in platelet
cyclic AMP concentration was not apparent between beige and normal mice after
prostacyclin stimulation. Platelet endoperoxide synthesis measured by quantification of
thromboxane B2, was normal in beige mice.
Protein phosphorylation patterns in mouse platelets were similar to those seen in human platelets.
Thrombin and
collagen-induced [32P] phosphorylation of 40- and 20-kD
proteins in platelets from normal and beige mice was similar. Results indicate that the biochemical defect(s) in platelet function in beige mice is partially attributable to
storage pool deficiency and does not result in an absolute defect in phosphorylation of 40- and 20-kD
proteins.