Phenotypes associated with this allele

• Allele Symbol: Shc1^tm1Pgp
• Allele Name: targeted mutation 1, Pier G Pelicci
• Allele ID: MGI:2159438
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Shc1^tm1Pgp/Shc1^tm1Pgp	involves: 129	MGI:3513556

Genotype
MGI:3513556

hm1

• Allelic Composition: Shc1^tm1Pgp/Shc1^tm1Pgp
• Genetic Background: involves: 129

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

mortality/aging

extended life span ( J:58535 )

• homozygotes display a ~30% increase in median lifespan, in the absence of any obvious defective phenotype

cardiovascular system

decreased susceptibility to atherosclerosis ( J:81977 )

• chronic 21% HFD increases the aortic cumulative early lesion area only by 3% in homozygous mutants versus 21% in wild-type mice

atherosclerotic lesions ( J:81977 )

• when subjected to a chronic 21% HFD, both mutant and wild-type males develop only very early atherosclerotic lesions in the range of 20-250 m2

• hypercholesterolemic mutants exhibit decreased levels of isoprostanes and oxidized LDLs and a significant reduction of oxidation-specific epitopes and foam cells in the arterial wall, indicating protection against oxidative stress and early lesion formation

• also, male homozygotes show a significant reduction of vascular apoptosis in their early atherogenic lesions relative to wild-type males

increased vasodilation ( J:81977 )

• male homozygotes fed a 21% HFD show an ~30% increase in acetylcholine (-6.0 log M)-induced vascular relaxation in abdominal aortic rings relative to wild-type males

cellular

decreased cellular sensitivity to oxidative stress ( J:58535 )

• at 10 weeks of age, homozygotes show increased resistance to paraquat toxicity (an inducer of oxidative stress), demonstrated by a ~40% increase in mean survival after i.p. administration of paraquat

decreased cellular sensitivity to hydrogen peroxide ( J:58535 , J:81977 )

• mutant MEFs are more resistant to apoptosis induced by hydrogen peroxide treatment compared to wild-type MEFs (J:58535)

• mutant endothelial cells are also more resistant to hydrogen peroxide-induced apoptosis relative to wild-type (J:81977)

decreased cellular sensitivity to ultraviolet irradiation ( J:58535 , J:81977 )

• mutant MEFs are more resistant to apoptosis induced by UV radiation compared to wild-type MEFs (J:58535)

• mutant endothelial cells are also more resistant to UV-induced apoptosis relative to wild-type (J:81977)

oxidative stress ( J:81977 )

• when chronically fed a 21% high-fat diet (HFD, male homozygotes show reduced systemic oxidative stress (isoprostanes) and susceptibility of LDL to ex vivo oxidation compared with wild-type males

growth/size/body

growth/size/body region phenotype ( J:58535 )

N • homozygotes exhibit no significant differences in body weight or food consumption relative to wild-type

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:81977 )

N • when fed a 21% HFD, both mutant and wild-type males display a similar (~3-fold) increase in serum cholesterol levels

N • this HFD-induced plasma hypercholesterolemia is comparable to that observed in 129/Sv mice subjected to a 15% fat diet

muscle

increased vasodilation ( J:81977 )

• male homozygotes fed a 21% HFD show an ~30% increase in acetylcholine (-6.0 log M)-induced vascular relaxation in abdominal aortic rings relative to wild-type males