Phenotypes associated with this allele

• Allele Symbol: Fbn1^tm1Rmz
• Allele Name: targeted mutation 1, Francesco Ramirez
• Allele ID: MGI:1934905
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fbn1^tm1Rmz/Fbn1^tm1Rmz	involves: 129S4/SvJae * C57BL/6J	MGI:3619415

Genotype
MGI:3619415

hm1

• Allelic Composition: Fbn1^tm1Rmz/Fbn1^tm1Rmz
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:43199 , J:91815 )

• all die suddenly of cardiovascular complications before weaning age (J:43199)

• mice die at P7-P10 from aortic dissection and rupture (J:91815)

cardiovascular system

abnormal aorta morphology ( J:43199 )

• 6 of 9 show thinning of the wall of the proximal ascending aorta, suggesting aneurismal dilation

• exhibit focal fragmentation of elastic fibers, accumulation of amorphous matrix and dissection of blood into the aortic media (aortic dissection)

• chronic lesions in the aorta show expansion of the intramural thrombus, recruitment of inflammatory cells and an adventitial reaction of cellular proliferation when the full thinckness of the wall is breached

aortic sinus aneurysm ( J:43199 )

• 6 of 9 show thinning of the wall of the proximal ascending aorta, suggesting aneurismal dilation

aortic dissection ( J:43199 )

• 6 of 9 exhibit dissection of blood into the aortic media (aortic dissection)

abnormal lung vasculature morphology ( J:43199 )

• pulmonary vessels occasionally appear distended and hyalinized

hemopericardium ( J:43199 )

hemothorax ( J:43199 )

lung hemorrhage ( J:43199 )

• pulmonary hemorrhage

respiratory system

abnormal lung vasculature morphology ( J:43199 )

• pulmonary vessels occasionally appear distended and hyalinized

hemothorax ( J:43199 )

lung hemorrhage ( J:43199 )

• pulmonary hemorrhage

abnormal lung development ( J:91815 )

• mice exhibit enhanced TGF-beta signaling and impaired distal airspace septation

• at P7, dysregulation of TGF-beta activation and signaling results in increased apoptosis, but normal cell proliferation, in the developing lung

• treatment with TGF-beta neutralizing antibody attenuates apoptosis and improves alveolar septation in vivo

• proximal airway caliber and vasculature are grossly normal

• no differences in airway cell differentiation or elastin deposition are observed

impaired lung alveolus development ( J:91815 , J:137934 )

• at P9, rare secondary alveolar septae are observed, indicating impaired distal alveolar septation (J:91815)

• active TGF-beta signaling is enhanced in mutant lungs by a factor of 25 relative to wild-type controls; neutralizing antibody to TGF-beta rescues the lung maturation phenotype, suggesting that TGF-beta is a physiologic inhibitor of alveolar septation (J:91815)

• at P5, expression of NeuroD1 protein (a candidate septation mediator) is reduced by 5-fold relative to that in wild-type controls; treatment with TGF-beta neutralizing antibody causes only a 1.5-fold induction of NeuroD1 expression , suggesting a minor contribution of NeuroD1 deficiency to the lung phenotype (J:137934)

abnormal pulmonary neuroendocrine body morphology ( J:137934 )

• at P5, the average size of mutant pulmonary NEBs is ~30% smaller than that in wild-type mice, suggesting impaired neuroendocrine maturation

increased number of pulmonary neuroendocrine bodies ( J:137934 )

• at P5, the total number of pulmonary neuroendocrine foci (composed of NEBs and PNECs) is modestly higher than that of wild-type controls

abnormal pulmonary alveolus morphology ( J:43199 )

• mice occasionally exhibit multifocal distension and coalescence of alveoli

overexpanded pulmonary alveolus ( J:91815 , J:137934 )

• mice display progressive distal airspace enlargement, apparent from P1 (J:91815)

• at P5, distal airspaces are enlarged, as shown by a significant increase in mean linear intercept (J:137934)

• the airspace lesion is progressive throughout postnatal life (J:137934)

abnormal pulmonary interalveolar septum morphology ( J:91815 , J:137934 )

• at P9, rare secondary alveolar septae are observed (J:91815)

• alveolar septation is impaired in the immediate postnatal period (J:137934)

emphysema ( J:43199 )

• mice occasionally exhibit multifocal distension and coalescence of alveoli suggesting emphysema

homeostasis/metabolism

hemopericardium ( J:43199 )

abnormal arterial thrombosis ( J:43199 )

• exhibit thrombosis of the aortic wall

endocrine/exocrine glands

increased solitary pulmonary neuroendocrine cell number ( J:137934 )

• at P5, the total number of pulmonary neuroendocrine foci (composed of NEBs and PNECs) is modestly higher than that of wild-type controls

nervous system

increased solitary pulmonary neuroendocrine cell number ( J:137934 )

• at P5, the total number of pulmonary neuroendocrine foci (composed of NEBs and PNECs) is modestly higher than that of wild-type controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:43199