Phenotypes Associated with This Genotype

Genotype
MGI:3619460

• Allelic Composition: Fbn1^tm2Rmz/Fbn1^tm2Rmz
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Clinical view of wild-type and Fbn1^tm2Rmz/Fbn1^tm2Rmz littermates

mortality/aging

premature death ( J:54081 , J:91815 )

• 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

abnormal blood vessel morphology ( J:54081 )

• loss of structural integrity of vessel wall

• newborns exhibit normal vasculature however with age develop late-onset vascular disease

abnormal aorta morphology ( J:54081 )

abnormal aorta tunica adventitia morphology ( J:54081 )

• 12 of 20 exhibit adventitia hyperplasia with inflammation

abnormal aorta tunica intima morphology ( J:54081 )

• 6 of 20 exhibit intimal hyperplasia

abnormal aorta tunica media morphology ( J:54081 )

• 9 of 20 exhibit medial necrosis and vasculitis

• 8 of 20 exhibit medial calcification

aortic elastic tissue lesions ( J:54081 )

calcified aorta ( J:54081 )

• 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

aortic aneurysm ( J:54081 )

• in the most advanced aneurysms, an infiltrate of macrophages is found at the adventitial surface with extension into an obliterated tunica media

hemorrhage ( J:54081 )

• hemomediastinum

hemopericardium ( J:54081 )

hemothorax ( J:54081 )

aortitis ( J:54081 )

• 9 of 20 exhibit medial aorta vasculitis

respiratory system

hemothorax ( J:54081 )

lung inflammation ( J:91815 )

• peribronchial inflammation by 6 months of age

impaired lung alveolus development ( J:91815 )

• 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

overexpanded pulmonary alveolus ( J:91815 )

• significant airspace dilatation by 6 months of age

emphysema ( J:91815 )

• by 6 months of age, airspace dilatation is associated with destructive changes, peribronchial inflammation, and increased expression of matrix metalloproteases, indicating emphysema

respiratory distress ( J:54081 )

• mice with kyphosis and diaphragmatic hernia exhibit respiratory distress

skeleton

increased length of long bones ( J:54081 )

• long bones are at most 10% longer than in wild-type

abnormal rib morphology ( J:54081 )

• dramatic overgrowth of the ribs

kyphosis ( J:54081 )

decreased bone mineral density ( J:187484 )

decreased bone volume ( J:187484 )

decreased bone trabecula number ( J:187484 )

growth/size/body

enlarged chest ( J:54081 )

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

immune system

aortitis ( J:54081 )

• 9 of 20 exhibit medial aorta vasculitis

lung inflammation ( J:91815 )

• peribronchial inflammation by 6 months of age

muscle

diaphragmatic hernia ( J:54081 )

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

homeostasis/metabolism

hemopericardium ( J:54081 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:54081