Mouse Genome Informatics
hm
    Fbn1tm2Rmz/Fbn1tm2Rmz
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       

Clinical view of wild-type and Fbn1tm2Rmz/Fbn1tm2Rmz littermates

mortality/aging
• mice die at an average age of 3.8 +/- 3.4 months (J:54081)
• mice die within 6-9 months of life due to aortic rupture (J:91815)

cardiovascular system
• loss of structural integrity of vessel wall
• newborns exhibit normal vasculature however with age develop late-onset vascular disease
• 12 of 20 exhibit adventitia hyperplasia with inflammation
• 6 of 20 exhibit intimal hyperplasia
• 9 of 20 exhibit medial necrosis and vasculitis
• 8 of 20 exhibit medial calcification
• in the most advanced aneurysms, an infiltrate of macrophages is found at the adventitial surface with extension into an obliterated tunica media
• calcification of intact elastic lamellae in the aorta is seen as early as 6 weeks of age
• calcified segments increase in frequency and coalesce over time
• hemomediastinum
• 9 of 20 exhibit medial aorta vasculitis

respiratory system
• peribronchial inflammation by 6 months of age
• impaired alveolar septation at 2 weeks of age
• immunostaining for active TGF-beta (a potential physiologic inhibitor of alveolar septation) is enhanced at 2 weeks of age
• significant airspace dilatation by 6 months of age
• by 6 months of age, airspace dilatation is associated with destructive changes, peribronchial inflammation, and increased expression of matrix metalloproteases, indicating emphysema
• mice with kyphosis and diaphragmatic hernia exhibit respiratory distress

skeleton
• long bones are at most 10% longer than in wild-type
• dramatic overgrowth of the ribs

growth/size
• increase in dorsal-ventral diameter of the chest because of overgrowth of the ribs

immune system
• 9 of 20 exhibit medial aorta vasculitis
• peribronchial inflammation by 6 months of age

muscle
• half of mice with severe kyphosis exhibit diaphragmatic hernia with thoracic migration of abdominal contents and respiratory distress

homeostasis/metabolism

Mouse Models of Human Disease
OMIM IDRef(s)
Marfan Syndrome; MFS 154700 J:54081