title: The fibrillin-1 hypomorphic mgR/mgR murine model of Marfan syndrome shows severe elastolysis in all segments of the aorta.
abstract: OBJECTIVE
  Fibrillin-1 hypomorphic mice (mgR/mgR) are accepted as a model of Marfan syndrome. Phenotypic investigations of this mouse have not previously included quantification of phenotypic features and detailed examinations of the histopathology other than in the ascending aorta.
  
  
  METHODS
  We developed a quantitative polymerase chain reaction assay to genotype the mice. Necropsy was performed on 50 male mice after natural death. We then sacrificed 10 mgR/mgR and 10 wild-type mice at 14-19 weeks to perform in vivo computed tomographic scans (n = 3) and microscopic examinations (n = 7). Four aortic segments (ascending, descending, pararenal, and infrarenal aorta) were excised. Each segment was divided into four subsegments and analyzed with Van Gieson staining. The number of elastin breaks and internal aortic diameter were determined twice in randomized, blinded fashion.
  
  
  RESULTS
  Computed tomographic scans of mgR/mgR mice revealed aneurysm formation in the ascending aorta and kyphoscoliosis. Elastolysis was present in all four aortic segments of mgR/mgR but was rarely observed in wild-type mice (P < .001). The diameter of the ascending aorta was larger in mgR/mgR than in wild-type mice (P = .01), but para- and infrarenal aortic diameter were even smaller in mgR/mgR mice (P < .001 and P = .01, respectively). Exploratory gene expression analysis showed a number of differentially expressed genes with overrepresentation of immune-related functions. Quantitative polymerase chain reaction analysis confirmed upregulation of selected genes in both the ascending aorta and the abdominal aorta.
  
  
  CONCLUSIONS
  Our findings suggest that mgR/mgR mice could be a useful model to study aortic abnormalities in segments other than the ascending aorta in order to understand the molecular mechanisms of aortic disease in Marfan syndrome.
authors.affiliation: Department of Cardiac Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Schwill
authors.forename: Philipp
authors.initials: P
authors.lastname: Seppelt
authors.forename: Johannes
authors.initials: J
authors.lastname: Grünhagen
authors.forename: Claus-Eric
authors.initials: CE
authors.lastname: Ott
authors.forename: Manfred
authors.initials: M
authors.lastname: Jugold
authors.forename: Arjang
authors.initials: A
authors.lastname: Ruhparwar
authors.forename: Peter N
authors.initials: PN
authors.lastname: Robinson
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Klaus
authors.initials: K
authors.lastname: Kallenbach
mesh_terms: D000818:Animals; D001011:Aorta / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D000071838:Fibrillin-1; D000071837:Fibrillins; D008297:Male; D008382:Marfan Syndrome; D051379:Mice; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines