Phenotypes associated with this allele

• Allele Symbol: Shc1^tm1Paw
• Allele Name: targeted mutation 1, Anthony Pawson
• Allele ID: MGI:2384189
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Shc1^tm1Paw/Shc1^tm1Paw	either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)	MGI:3622829

Genotype
MGI:3622829

hm1

• Allelic Composition: Shc1^tm1Paw/Shc1^tm1Paw
• Genetic Background: either: (involves: 129S1/Sv * 129X1/SvJ) or (involves: 129S1/Sv * 129X1/SvJ * CD-1)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:62182 )

• homozygotes die by E11.5

cardiovascular system

abnormal blood vessel morphology ( J:62182 )

• at E10.5, homozygotes display reduced complexity of the vascular architecture and increased vessel size

abnormal carotid artery morphology ( J:62182 )

• at E10.5, the mutant anterior carotid arteries appear relatively simple and dilated, with infrequent smaller branches

abnormal vascular endothelial cell morphology ( J:62182 )

• at E9.5, endothelial cells forming the endocardium in the mutant heart appear thinner and more elongated

decreased angiogenesis ( J:62182 )

• by E10.5, homozygotes display defective angiogenic remodeling (dilatation and reduced complexity of primary head vessels) associated with abnormal cell-cell contacts

• TEM revealed weak cell-to-cell contacts between the abluminal endothelial cell surfaces and surrounding support cells, and also between VSMCs and their neighbors

abnormal vitelline vasculature morphology ( J:62182 )

• at E9.5, mutant yolk sacs display disrupted vasculature with large and uniformly sized lumens and disorganized mesodermal angioblast-derived blood islands

abnormal vascular smooth muscle morphology ( J:62182 )

• at E10.5, homozygotes show impaired association of mutant periendothelial VSMCs with the endothelium

vascular smooth muscle hypoplasia ( J:62182 )

• at E10.5, homozygotes scattered and frequently reduced VSMCs throughout the entire vascular system

• a relative absence of VSMC-coating branches is noted in the head (anterior carotid arteries)

abnormal vein morphology ( J:62182 )

• at E10.5, the mutant primary head veins are dilated

heart vascular congestion ( J:62182 )

• by E11.5, mutant hearts and cardiac outflow tracts are congested with blood

trabecula carnea hypoplasia ( J:62182 )

• by E10.5, homozygotes display severely reduced trabeculation in the ventricle

thin myocardium ( J:62182 )

• by E10.5, homozygotes exhibit a thin myocardium associated with reduced trabeculation

abnormal atrioventricular cushion morphology ( J:62182 )

• by E10.5, homozygotes display poorly developed (hypoplastic) endocardial cushions

• reduced cell contacts are noted between mesenchymal cells in the endocardial cushions and the cardiac myocytes of the heart wall

atrioventricular cushion hypoplasia ( J:62182 )

abnormal heart left ventricle morphology ( J:62182 )

• at E10, homozygotes show an abnormally shaped left ventricle

decreased heart left ventricle wall thickness ( J:62182 )

• at E10, homozygotes display a thin-walled left ventricle

enlarged pericardium ( J:62182 )

• by E10.5, mutant embryos frequently display an enlarged pericardium but are equivalent in size to wild-type embryos

decreased cardiac muscle contractility ( J:62182 )

• by E10.5, homozygotes show poor heart contractility

embryo

abnormal vitelline vasculature morphology ( J:62182 )

• at E9.5, mutant yolk sacs display disrupted vasculature with large and uniformly sized lumens and disorganized mesodermal angioblast-derived blood islands

pale yolk sac ( J:62182 )

• by E11.5, all homozygotes appear necrotic with pale yolk sacs

muscle

abnormal vascular smooth muscle morphology ( J:62182 )

• at E10.5, homozygotes show impaired association of mutant periendothelial VSMCs with the endothelium

vascular smooth muscle hypoplasia ( J:62182 )

• at E10.5, homozygotes scattered and frequently reduced VSMCs throughout the entire vascular system

• a relative absence of VSMC-coating branches is noted in the head (anterior carotid arteries)

trabecula carnea hypoplasia ( J:62182 )

• by E10.5, homozygotes display severely reduced trabeculation in the ventricle

thin myocardium ( J:62182 )

• by E10.5, homozygotes exhibit a thin myocardium associated with reduced trabeculation

decreased cardiac muscle contractility ( J:62182 )

• by E10.5, homozygotes show poor heart contractility

cellular

abnormal cell morphology ( J:62182 )

• mutant MEFs plated on fibronectin show an aberrant rounded morphology, including an increased number of small focal complexes and a disorganized, depolarized actin cytoskeleton

abnormal actin cytoskeleton morphology ( J:62182 )

• mutant MEFs plated on fibronectin show a disorganized, depolarized actin cytoskeleton

abnormal cell physiology ( J:62182 )

• mutant MEFs and embryos show impaired sensitivity to growth factors

• MAPK activation is specifically impaired in regions of mutant embryos that undergo angiogenic remodeling

abnormal cell adhesion ( J:62182 )

• at E10.0, homozygotes show impaired adhesive contact of the endothelium with adjacent ECM components and support cells

• reduced cellular adhesion is also noted in the outflow tract and yolk sac