Phenotypes Associated with This Genotype

Genotype
MGI:5295754

• Allelic Composition: Lmna^tm1.1Otin/Lmna⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

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

mortality/aging

premature death ( J:177632 , J:177575 )

• mutants exhibit an average lifespan of 242 days (J:177632)

growth/size/body

weight loss ( J:177632 )

• mutants start to lose weight at around 8 months of age

homeostasis/metabolism

abnormal blood homeostasis ( J:211388 )

• 8-fold decrease in plasma ATP concentrations

• 9-fold decrease in plasma pyrophosphate concentrations

• however, no differences in plasma phosphorus or calcium levels are seen

decreased circulating glucose level ( J:177632 )

• at 8 months of age, heterozygotes show a decrease in serum glucose concentrations

increased circulating alkaline phosphatase level ( J:211388 )

• 29.5% higher levels of plasma alkaline phosphatase activity than controls

cellular

abnormal cell nucleus morphology ( J:177632 , J:177575 )

• mutants show nuclear abnormalities due to progerin accumulation (J:177632)

• MEFs have more misshapen nuclei with nuclear blebs than wild-type MEFs (J:177575)

cardiovascular system

calcified aorta ( J:211388 )

• medial calcification in aortic arch and thoracic aorta at 30-34 weeks of age

calcified thoracic aorta ( J:211388 )

calcified aortic arch ( J:211388 )

abnormal vascular smooth muscle physiology ( J:211388 )

• primary cultures of vascular smooth muscle cells from aortic tissue show a lower capacity to inhibit calcium deposition than control cells when incubated in calcifying medium

• aortic vascular smooth cells exhibit impaired capacity to synthesize extracellular pyrophosphate, show lower levels of extracellular ATP and intracellular ATP indicating impaired ATP synthesis, and have a lower COX:CS ratio indicating impaired mitochondrial function

muscle

abnormal vascular smooth muscle physiology ( J:211388 )

• primary cultures of vascular smooth muscle cells from aortic tissue show a lower capacity to inhibit calcium deposition than control cells when incubated in calcifying medium

• aortic vascular smooth cells exhibit impaired capacity to synthesize extracellular pyrophosphate, show lower levels of extracellular ATP and intracellular ATP indicating impaired ATP synthesis, and have a lower COX:CS ratio indicating impaired mitochondrial function

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
progeria		DOID:3911	OMIM:176670	J:211388