| Popis: |
The mechanisms which determine and regulate platelet size are unknown. By phase microscopy, we serendipitously observed that Wistar/Furth (W/F) rats had macrothrombocytopenia. In this study, we have characterized and compared platelets and megakaryocytes (MK) of W/F rats to those of Wistar (W), Long-Evans hooded (LE) and Sprague-Dawley (SD) rats. In addition, we have examined the mode of inheritance of this W/F rat platelet abnormality. Average platelet count of W/F rats was only 312 ± 57 x 103/mm3 compared to 1086 ± 68, 868 ± 91 and 926 ± 82 x 103/mm3 respectively for W, LE and SD rats. Mean platelet volume (MPV) of W/F rats (8.1 ± 1.4 fl) was twice that of W (4.0 ± 0.2 fl), LE (4.2 ± 0.3 f1) and SD (4.1 ± 0.2 f1) rats. However, average MK diameter and DNA content distribution of W/F rats were not significantly different than those of LE rats. Average MK concentration was somewhat lower (4.5 MK/high power field) in the W/F strain compared to that of LE rats (6.6 MK/HPF). Maze-like membrane formations were observed in W/F MK and platelets by electron microscopy. Reciprocal crosses of W/F and LE rats resulted in offspring with MPVs (4.2 fl) and platelet counts like those of LE rats, indicating that the macrothrombocytopenic trait is recessive in its inheritance. Reciprocal marrow transplants between the W/F and LE strains resulted in MPVs like those of the donor strain indicating that the macrothrombocytopenia is an intrinsic marrow abnormality of the W/F strain. Analysis of W/F platelets by two-dimensional polyacrylamide gel electrophoresis revealed two readily detectable differences from those of W and LE rats: (1) absence of a protein of MW of 41,000 and pi of 6.35 and (2) presence of a protein of MW of 35,000 and pi of 5.9. In summary, the W/F rat has a hereditary macrothrombocytopenia which is recessive in nature and not due to differences in MK size or DNA content. These results suggest that the macrothrombocytopenia of W/F rats results from formation of fewer platelets per MK, possibly due to a qualitative or quantitative defect in some component necessary for proper subdivision of megakaryocyte cytoplasm into platelets. |
