Content area
Abstract
Coxsackievirus B3 (CVB3) contributes to the development of myocarditis, an inflammatory heart disease that predominates in males, and infection is a cause of unexpected death in young individuals. Although gonadal hormones contribute significantly to sex differences, sex chromosomes may also influence disease. Increasing evidence indicates that Chromosome Y (ChrY) genetic variants can impact biological functions unrelated to sexual differentiation. Using C57BL/6J (B6)-ChrY consomic mice, we show that genetic variation in ChrY has a direct effect on the survival of CVB3-infected animals. This effect is not due to potential Sry-mediated differences in prenatal testosterone exposure or to differences in adult testosterone levels. Furthermore, we show that ChrY polymorphism influences the percentage of natural killer T cells in B6-ChrY consomic strains but does not underlie CVB3-induced mortality. These data underscore the importance of investigating not only the hormonal regulation but also ChrY genetic regulation of cardiovascular disease and other male-dominant, sexually dimorphic diseases and phenotypes.
Details
1 Department of Medicine and
2 Department of Molecular Microbiology and Immunology and; Graduate Program in Pathobiology, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912
3 Department of Pathology, University of Vermont, Burlington, Vermont 05405
4 Department of Medicine and; Department of Pathology, University of Vermont, Burlington, Vermont 05405; Center for Nuclear Receptors and Cell Signaling, University of Houston, Houston, Texas 77204