Abstract 20315: Sexual Dimorphism in a Marfan Syndrome Mouse Model

    loading  Checking for direct PDF access through Ovid

Abstract

Objective: The effect of sexual dimorphism on aortic pathology in mouse models of Marfan Syndrome has not been defined. Therefore, we determined differences in aortic diameter expansion between sexes in fibrillin-1 hypomorphic (FBN1mgR/mgR) mice.

Methods and Results: Ascending aortic diameters from male and female FBN1mgR/mgR mice and their wild type littermates were assessed every 4 weeks from 6 to 18 weeks of age by ultrasound. Measurements were taken luminal edge to luminal edge in diastole. Differences in aortic diameters between male and female FBN1mgR/mgR mice were detected as early as 6 weeks of age (1.79 ± 0.11 vs 1.40 ± 0.12 mm; p = 0.025) while there was no significant diameter differences between sexes of wild type littermates (1.11 ± 0.12 vs 1.10 ± 0.12 mm; p = 0.94). At 18 weeks of age, differences of aortic diameters between male and female FBN1mgR/mgR mice increased further (2.61 ± 0.21 vs 1.74 ± 0.17 mm; p = 0.006), while there were no significant differences between sexes of wild type littermates (1.35 ± 0.17 vs 1.16 ± 0.17 mm; p = 0.44). External aortic diameter measured after termination at 18 weeks correlated with in vivo ultrasound measurements (R^2 = 0.955). Male FBN1mgR/mgR mice had significantly greater aortic dilation compared to their female littermates (2.45 ± 0.17 vs 1.55 ± 0.15 mm; p = 0.001). In contrast, aortic diameters were not different between sexes of wild type littermates (1.16 ± 0.13 vs 1.06 ± 0.13 mm; p = 0.56). In addition to increased aortic diameter, death due to aortic rupture by 18 weeks was more frequent in male FBN1mgR/mgR mice than in female FBN1mgR/mgR mice (50% vs 20%).

Conclusions: FBN1mgR/mgR mice exhibit sexually dimorphic ascending aortic diameters as early as 6 weeks of age. This sex difference increased with age in FBN1mgR/mgR mice, while their wild type littermates do not exhibit significant difference. Subsequent studies using this model of Marfan Syndrome should state the sex of mice.

Related Topics

    loading  Loading Related Articles