Imaging-based age- and sex-related cardiovascular and skeletal phenotypes in Fbn1C1041G/+ mice

Marfan syndrome is a multisystem connective tissue disorder with age- and sex-related phenotypic variability. This study characterized early cardiovascular, valvular, transmitral filling, and skeletal phenotypes in Fbn1 C1041G/ + mice. Male and female wild-type and Fbn1 C1041G/ + mice were examined in independent age-specific cohorts from 4 to 20 weeks of age. Transthoracic echocardiography was used to measure aortic root and ascending aortic diameters, anterior mitral leaflet length, and mitral inflow Doppler parameters. Lateral X-ray imaging was used to quantify kyphosis angle. Fbn1 C1041G/ + mice of both sexes showed age-related aortic enlargement, with segment-specific sex-related heterogeneity involving the annulus and sinus. In mutant mice, anterior mitral leaflet elongation was detected from 8 weeks in males and at 20 weeks in females. Reduced E-wave velocity and E/A ratio were observed in both sexes at 4 weeks, with E-wave velocity remaining lower at most subsequent ages and a lower E/A ratio present at all ages; A-wave velocity did not differ between genotypes at any examined age. Reduced kyphosis angle was detected from 4 weeks in females and from 12 weeks in males. These findings show that early Fbn1-related phenotypes follow organ-specific age-related patterns, supporting age-resolved and sex-stratified assessment in preclinical Marfan syndrome studies.