Inherited abnormalities in platelet organelles and platelet formation and associated altered expression of low molecular weight guanosine triphosphate-binding proteins in the mouse pigment mutant gunmetal.
Gunmetal (gm/gm) is a recessively inherited mouse pigment dilution mutant that has high mortality and poor reproductive rates. In these studies, several hematologic defects were found associated with the mutation, including prolonged bleeding times, together with thrombocytopenia and increased platelet size. A unique feature is the presence of simultaneous abnormalities in two platelet organelles, dense granules and alpha-granules. The dense granule component serotonin is present at about half the normal concentration, as are visible dense granules. Three alpha-granule components (fibrinogen, platelet factor 4, and von Willebrand factor) are also significantly reduced. Thus, in several respects the gunmetal mutant resembles the human gray platelet syndrome. A novel abnormality in expression of low molecular weight guanosine triphosphate (GTP)-binding proteins occurs in platelets of gunmetal. In Western blot assays, two additional GTP-binding proteins of 28.5 and 25 Kd were detected. The abnormal expression of GTP-binding proteins is, like the hematologic defects, genetically recessive and is tissue specific. Liver, kidney, brain, spleen, macrophages, and neutrophils have normal GTP-binding protein expression. The additional GTP-binding proteins are soluble. The data indicate that platelet formation and platelet organelle biogenesis are under common genetic control and that abnormal regulation of GTP-binding proteins may affect one or both processes.
Swank
R T
RT
Dept. of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY 14263.
Jiang
S Y
SY
Reddington
M
M
Conway
J
J
Stephenson
D
D
McGarry
M P
MP
Novak
E K
EK
D000818:Animals; D001760:Bleeding Time; D001791:Blood Platelet Disorders / Q000097:blood* / Q000235:genetics*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D005966:Glucuronidase / Q000097:blood; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008817:Mice, Mutant Strains; D008970:Molecular Weight; D015388:Organelles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D010859:Pigmentation Disorders / Q000235:genetics*; D012701:Serotonin / Q000097:blood; D013045:Species Specificity; D013917:Thrombin / Q000494:pharmacology; D001616:beta-Galactosidase / Q000097:blood
D012701:Serotonin; D001616:beta-Galactosidase; D005966:Glucuronidase; D013917:Thrombin; D019204:GTP-Binding Proteins