Abstract 13282: The Fibrillin-1-Deficient mgR/mgR Murine Model Of Marfan Syndrome Shows Severe Elastolysis in All Segments of the Aorta
The Fibrillin1 hypomorphic mgR/mgR mouse is an accepted and widely used model of Marfan syndrome. Phenotypic investigations of this mouse have so far not included detailed examinations of the histopathology other than in the ascending aorta. In this work we present for the first time a quantitative analysis of the phenotypic features of the aorta of the mgR/mgR mouse. We first developed a quantitative real-time PCR (RT-PCR) assay to genotype the mice. RT-PCR was performed in 383 littermates. Necropsy was performed on 50 male mice after natural death; 49/50 of these mice had been found to be homozygous for the mgR allele by RT-PCR, and these mice were found to have died from rupture of the thoracic aorta. We then sacrificed 7 homozygous mgR/mgR and 7 wild-type mice at the age of 14-19 weeks. Four aortic segments were excised, the ascending (A), the descending (B), the pararenal (C) and infrarenal (D) aorta. Each segment was divided into four subsegments and analyzed with van Gieson staining. The numbers of breaks and the internal diameter of the aorta were determined twice in a randomized and blinded fashion. CT-Scan was used to investigate mgR/mgR (n=3) and wild-type mice (n=3). Mann Whitney test was used for statistical analysis. CT scans of mgR/mgR mice revealed aneurysms of the ascending aorta and severe kypho-scoliosis. Elastolysis, adjacent breaks and breakthroughs were present in all four aortic segments of mgR/mgR and were rarely observed in wild-type mice (p=0.001). There were two times as many breaks in aortic segment A than in the other three segments of mgR/mgR mice (p=0.01). Segment A was larger in mgR/mgR than in wild-type mice (p=0.01) but the diameter of segments C and D were smaller in mgR/mgR than in wild-type mice (p=0.001; p=0.01). In conclusion, the highest density of elastin breaks was found in the ascending aorta, but elastin breaks were commonly found in all aortic segments of mgR/mgR mice. Interestingly, the diameter of the para- and infrarenal aortic segments was significantly smaller in mgR/mgR than in wild-type littermates of the same age. Our findings suggest that the mgR/mgR mouse could be a useful model to study aortic abnormalities in segments other than the ascending aorta to understand the molecular mechanisms of aortic dissection in Marfan syndrome.
- © 2011 by American Heart Association, Inc.