Inherited prolonged bleeding time and platelet storage pool deficiency in the subtle gray (sut) mouse.

A high proportion of mouse mutants with diluted pigmentation have severely prolonged bleeding times due to platelet storage pool deficiency. The deficiency is associated with concomitant abnormalities in platelet dense granules and coat pigment granules. The coat color of the subtle gray (sut) mouse is diluted to a relatively minor degree. Analysis of platelet serotonin concentration established that this dense granule component similarly is reduced a relatively small amount in this mutant. The subtle gray mouse thus allowed a test of the hypothesis that relatively small changes in platelet dense granule contents may cause discernible increases in bleeding times. Bleeding times of mutant mice were significantly prolonged (3.4-fold) in comparison with those in normal sut/+ controls. These bleeding times were significantly reduced in comparison with other mouse pigment dilution mutants with more severe storage pool deficiency. These results establish the subtle gray mouse as an appropriate animal model for mild storage pool deficiency and human Hermansky-Pudlak syndrome. They indicate, together with related experiments, that bleeding times are highly sensitive to concentrations of platelet dense granule components such as serotonin.