C3H mice have larger spleens, lower platelet counts, and shorter platelet lifespans than C57BL mice: an animal model for the study of hypersplenism.

: Several studies have shown that C3H mice have a modal megakaryocyte ploidy class of 32N as opposed to the 16N found in all other mouse strains tested. In addition to higher megakaryocyte DNA content, C3H mice are characterized by greater 35S-sulfate incorporation into platelets but somewhat lower platelet counts than C57BL mice. The aim of this study was to determine the etiology of mild thrombocytopenia in C3H mice. Several studies have indicated that an increase in platelet 35S incorporation parallels increased megakaryocyte ploidy. Thus the higher 35S incorporation by C3H mouse platelets is likely related to their higher megakaryocyte ploidy, but these differences do not explain the lower platelet counts observed in C3H mice. To elucidate the paradox of relatively low platelet counts in C3H mice despite elevated platelet 35S incorporation, we performed a hematological evaluation (including assessment of platelet counts and lifespans) and measured (relative) spleen size in C3H and C57BL mice. Our data confirm earlier reports of significantly lower platelet counts in C3H mice (p < 0.0005) compared with C57BL mice. We also found that C3H mice have larger spleens (p < 0.0005) than C57BL mice. Other groups of C3H and C57BL mice were splenectomized to determine the role of the spleen in decreasing platelet counts in C3H mice compared with C57BL mice. C3H mice had an average platelet lifespan of 4.8 days, which was significantly shorter (p < 0.01) than the 5.7-day platelet lifespan observed in normal C57BL mice. Platelet lifespans for splenectomized C3H mice were significantly (p < 0.005) longer than those found in intact C3H control mice, but splenectomy of C57BL mice had no effect on their platelet lifespans (p < 0.40). The lengthened platelet lifespans of splenectomized C3H mice indicate that the spleens of C3H mice were sequestering or destroying platelets at a faster rate than the spleens of C57BL mice. These data lead to the hypothesis that the relatively large spleens of C3H mice produce mild thrombocytopenia with increased platelet production (shorter platelet lifespan) compared with spleens of C57BL mice.