Genetic variation in ChrY modifies the sexual dimorphism in myocarditis and leads to a sex bias in EAE severity. (A) Male and female mice from WT B6 and male mice from four B6–ChrY consomic strains were infected with 50 PFU CVB3 and their hearts were evaluated for myocarditis. Heart score of female B6 was subtracted from the heart score for male WT B6 and each B6–ChrY consomic strain. Labeling on the x-axis represents the strain donating ChrY to B6. Results are representative of three individual experiments. n ≥ 5 mice per strain. Significance determined by one-way ANOVA and Dunnett's multiple comparison test. (*) P ≤ 0.05; (****) P ≤ 0.0001. (B) Female B6 and male B6–ChrY consomic mice were immunized with MOG35–55 using the 2× protocol and the clinical score was monitored over 30 d. The significance of the differences in disease course among the strains was determined by two-way ANOVA (interaction [F = 1.18; DFn = 319; DFd = 7770; P = 0.02], day post-injection [F = 132.8; DFn = 29; DFd = 7770; P < 0.0001], and strain [F = 23.5; DFn = 11; DFd = 7770; P < 0.0001]). (C) The significance of the differences in disease course between B6 female mice and each B6–ChrY consomic line was determined as described in Supplemental Figure S2 and grouped accordingly. The significance of the differences in sexual dimorphism among the groups was determined by comparing the best-fit values for the F < M and F > M grouping against the F = M group and by two-way ANOVA (interaction [F = 1.14; DFn = 348; DFd = 8880; P = 0.04], day post-injection [F = 155.5; DFn = 29; DFd = 8880; P < 0.0001], and strain [F = 22.58; DFn = 12; DFd = 8880; P < 0.0001]) followed by Holm-Sidak corrected post-hoc multiple comparisons. (*) P ≤ 0.05; (****) P ≤ 0.0001.
