Mice homozygous for the Rabggtagm allele are grayish-black on a non-agouti background due to pigment dilution. Eye color is not affected. Homozygotes have reduced viability and do not breed well. These mutants have a prolonged bleeding time. Although gunmetal mice have an increased number of megakariocytes, they have about half the number platelets found in wildtype siblings. This decrease in platelet number results from a slower rate of platelet synthesis. These platelets are heterogeneous in size and are larger than normal, but have fewer dense granules per platelet and approximately half of the normal level of serotonin. The prolonged bleeding time and decreased platelet count and volume can be transferred to wildtype mice through bone marrow transplantion. Likewise bone marrow transplants from wildtype mice reversed the platelet deficiency in gunmetal recipients. Western blots of platelet extracts showed a decrease in fibrinogen, von Willebrand factor, and platelet factor 4, but von Willebrand factor in serum plasma is increased in these mutants. Electron microscopy of megakaryocytes from these mutants revealed that the demarcation membranes are not homogeneously distributed and an increased percentage of megakaryocytes are undergoing emperipolesis. This emperipolesis can produce false increases in apparent ploidy in flow cytometry of these megakariocytes. Gunmetal platelets also have unusual membrane complexes including elongated, striated inclusion granules and profiles of Golgi complex. In keeping with the expression pattern of Rab27, no abnormalities were detected in white or red blood cells. (Dickie, 1964; Swank et al., 1993; Novak et al., 1995; McGarry et al., 1999.)
