title: Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci.
abstract: Seven mouse pigment mutants, which have alterations at distinct genes, are known to have a defect in kidney lysosomal enzyme secretion. Two of these, beige and pale ear, have a bleeding abnormality associated with a deficiency in the number of platelet dense granules. In the present study, five other mutants with defective lysosomal enzyme secretion--pearl, pallid, light ear, maroon, and ruby-eye--were likewise found to have abnormally prolonged bleeding times after experimental injury. Platelet counts were similar to those of normal mice, but the platelet dense granule components serotonin, adenosine triphosphate (ATP), and adenosine diphosphate (ADP) and morphologically identifiable dense granules were markedly reduced in these mutants. The capacity to accumulate exogenous 3H-serotonin in platelets was reduced 2-3-fold. Thrombin-stimulated secretion of 3H-serotonin was slightly decreased in all mutants. However, the seven mutants could be subdivided into three groups based on the degree of secretion of lysosomal enzymes after thrombin stimulation. Thus, all seven mouse pigment mutants have symptoms consistent with platelet storage pool deficiency and may serve as useful animal models for specific types of human platelet storage pool disease. Also, the results emphasize the genetic, morphological, and functional interrelatedness of three organelles: melanosomes, lysosomes, and platelet dense granules.
mesh_terms: D000818:Animals; D001791:Blood Platelet Disorders / Q000097:blood* / Q000150:complications / Q000235:genetics; D001792:Blood Platelets / Q000032:analysis / Q000201:enzymology / Q000648:ultrastructure; D002874:Chromosome Mapping; D003594:Cytoplasmic Granules / Q000032:analysis / Q000201:enzymology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008544:Melanocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL / Q000097:blood*; D009154:Mutation; D010859:Pigmentation Disorders / Q000097:blood* / Q000150:complications / Q000235:genetics; D012701:Serotonin / Q000378:metabolism
chemical_list: D012701:Serotonin