Phenotypes Associated with This Genotype

Genotype
MGI:6423604

• Allelic Composition: Lmna^tm1Bliu/Lmna^tm1Bliu; Tg(Tek-cre)1Ywa/0
• Genetic Background: involves: C57BL/6 * SJL

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

mortality/aging

premature death ( J:287256 )

• shorter median life span of 24 weeks

• mice treated with IS70, a recombinant AAV serotype 1 cassette with Sirt7 gene expression driven by a synthetic ICAM2 promoter show an expansion of median life span by 76%, from 25 to more than 44 weeks

premature aging ( J:287256 )

• mice show accelerated aging in various tissues/organs

• mice treated with IS70 ameliorates aging features

growth/size/body

weight loss ( J:287256 )

• mice exhibit weight loss

• mice treated with IS70 show a slight rescue in body weight loss

behavior/neurological

impaired exercise endurance ( J:287256 )

• running endurance is compromised

cardiovascular system

abnormal artery morphology ( J:287256 )

• severe fibrosis in the arteries

increased aorta wall thickness ( J:287256 )

• intima-media thickening

atherosclerotic lesions ( J:287256 )

• atherosclerosis is prominent, with aorta atheromatous plaque seen in all mice examined

decreased vascular endothelial cell number ( J:287256 )

• loss of CD31+ endothelial cells

decreased capillary density ( J:287256 )

abnormal physiological neovascularization ( J:287256 )

• limb perfusion after ischemia is blunted; defect in blood flow recovery is due to an impaired ability to form new blood vessels in the ischemic region indicating defective neovascularization

cardiac fibrosis ( J:287256 )

• severe fibrosis in the heart

dilated cardiomyopathy ( J:287256 )

• heart/body weight ratio is increased, indicating dilated cardiomyopathy

decreased cardiac output ( J:287256 )

• cardiac output is reduced in 7-8 month old mice

decreased heart left ventricle muscle contractility ( J:287256 )

• left ventricular ejection fraction and fractional shortening are reduced in 7-8 month old mice

decreased heart rate ( J:287256 )

• heart rate is reduced in 7-8 month old mice

abnormal vasodilation ( J:287256 )

• acetylcholine-induced thoracic aorta relaxation is compromised

homeostasis/metabolism

impaired exercise endurance ( J:287256 )

• running endurance is compromised

muscle

dilated cardiomyopathy ( J:287256 )

• heart/body weight ratio is increased, indicating dilated cardiomyopathy

decreased heart left ventricle muscle contractility ( J:287256 )

• left ventricular ejection fraction and fractional shortening are reduced in 7-8 month old mice

abnormal vasodilation ( J:287256 )

• acetylcholine-induced thoracic aorta relaxation is compromised

skeleton

decreased trabecular bone volume ( J:287256 )

• decrease in trabecular bone volume/tissue volume

decreased bone trabecula number ( J:287256 )

increased bone trabecular spacing ( J:287256 )

• increase in trabecular separation

decreased trabecular bone thickness ( J:287256 )

osteoporosis ( J:287256 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progeria		DOID:3911	OMIM:176670	J:287256