Phenotypes associated with this allele

• Allele Symbol: Fbn1^tm1Hcd
• Allele Name: targeted mutation 1, Harry C Dietz
• Allele ID: MGI:3690325
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fbn1^tm1Hcd/Fbn1^tm1Hcd	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3690326
ht2	Fbn1^tm1Hcd/Fbn1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3690327
cx3	Fbn1^tm1Hcd/Fbn1^+ Tgfb2^tm1Doe/Tgfb2^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:5444488

Genotype
MGI:3690326

hm1

• Allelic Composition: Fbn1^tm1Hcd/Fbn1^tm1Hcd
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

mortality/aging

postnatal lethality, complete penetrance ( J:91349 , J:94428 )

• die at P7 - P10 from aortic dissection (J:94428)

cardiovascular system

abnormal blood vessel morphology ( J:91349 )

• die from vascular catastrophe indistinguishable from mice homozygous for severe hypomorphic alleles

aortic dissection ( J:94428 )

abnormal mitral valve cusp morphology ( J:94428 )

• progressive increase in leaflet length and thickness during postnatal development first becoming significantly different from wild-type at P6.5 and P4.5, respectively

• the leaflet tips fold back and fuse to more proximal segments

• cells display increased proliferation and reduced apoptosis

• in utero treatment with TGFB neutralizing antibodies at E14.5 and E17.5 reduces mitral valve overgrowth

Genotype
MGI:3690327

ht2

• Allelic Composition: Fbn1^tm1Hcd/Fbn1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal aorta wall morphology ( J:91349 , J:188799 )

• progressive deterioration within the medial layer, with elastic fiber fragmentation and disarray of vascular smooth muscle cells begins around 2 months of age (J:91349)

• however, no intimal hyperplasia, aortic inflammation, or aortic dissection are detected and life span is similar to wild-type mice (J:91349)

abnormal aorta elastic fiber morphology ( J:91349 )

• progressive fragmentation of elastic fibers within the medial wall beginning around 2 months of age

• elastic fiber calcification is occasionally seen

increased aorta wall thickness ( J:94428 )

• gradual thickening of the wall due to excessive deposition of amorphous matrix and increase in the number of vascular smooth muscle cells

abnormal mitral valve cusp morphology ( J:94428 )

• progressive increase in leaflet length and thickness during postnatal development

• leaflet length and thickness are intermediate between homozygous mutant and wild-type mice

• cells display increased proliferation and reduced apoptosis

• in utero treatment with TGFB neutralizing antibodies at E14.5 and E17.5 rescues mitral valve morphology

mitral valve prolapse ( J:94428 )

• mitral valve prolapse and regurgitation at 9 months of age

increased heart left atrium size ( J:94428 )

• left atrium enlargement associated with mitral valve prolapse

increased heart left ventricle size ( J:94428 )

• left ventricle enlargement associated with mitral valve prolapse

mitral valve regurgitation ( J:94428 )

• mitral valve prolapse and regurgitation at 9 months of age

respiratory system

overexpanded pulmonary alveolus ( J:91349 )

• distal airspace widening without inflammation or tissue damage

skeleton

abnormal skeleton morphology ( J:91349 )

• gradual postnatal development of skeletal abnormalities similar to those in other hypomorphic mouse models of Marfan Syndrome

abnormal rib morphology ( J:91349 )

• postnatal overgrowth

kyphosis ( J:91349 )

• gradual postnatal development

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Marfan syndrome		DOID:14323	OMIM:154700	J:91349 , J:94428

Genotype
MGI:5444488

cx3

• Allelic Composition: Fbn1^tm1Hcd/Fbn1⁺; Tgfb2^tm1Doe/Tgfb2⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6J

cardiovascular system

abnormal aorta wall morphology ( J:188799 )

• elastic fiber fragmentation and greater collagen deposition within the medial compartment of the aortic wall is increased compared to either single heterozygote

dilated aorta bulb ( J:188799 )

• mutants show an increase in aortic root dimension at 2 and 4 months of age compared to either single heterozygote

• aortic dilatation is specific to the aortic root

aortic aneurysm ( J:188799 )

• aortic root aneurysm

growth/size/body

growth/size/body region phenotype ( J:188799 )

N • mutants exhibit normal body size and growth

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Loeys-Dietz syndrome		DOID:0050466		J:188799