Analysis Tools
mortality/aging
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• week-old homozygous pups are seen at approximately 50% lower frequency than expected
• however after weaning, surviving mice grown normally
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behavior/neurological
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• 13-month-old mice show decreased wire hang fall and reach scores, indicating impaired motor function
• however, no differences in rotarod performance or grip strength, and only a non-significant trend for lower activity levels and decreased time spent in the center of an open field
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• mice exhibit impaired exercise tolerance, with mice exhausting much earlier during moderate intensity exercise than wild-type mice
• during VO2 maximal exercise testing, mice reach or near lactate threshold during maximal exercise and achieve maximal VO2 consumption
• maximal VO2 during exercise testing is lower than wild-type mice
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cardiovascular system
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• increase in heart tissue weight and heart-to-body weight ratio
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• eccentric hypertrophy
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• eccentric hypertrophy with a dilated cardiomyopathy
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• in 12- to 15-month old mice
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• in 12- to 15-month old mice
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• 12- to 15-month old mice show lower ejection fraction
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• echocardiography of 12- to 15-month-old mice shows lower ejection fraction associated with lower cardiac output and stroke volume, and increased left ventricular wall mass
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growth/size/body
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• increase in heart tissue weight and heart-to-body weight ratio
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• eccentric hypertrophy
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homeostasis/metabolism
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• mice exhibit impaired exercise tolerance, with mice exhausting much earlier during moderate intensity exercise than wild-type mice
• during VO2 maximal exercise testing, mice reach or near lactate threshold during maximal exercise and achieve maximal VO2 consumption
• maximal VO2 during exercise testing is lower than wild-type mice
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• liver and cardiac palmitate oxidation is approximately 60% of wild-type suggesting reduced, but not absent, fatty acid oxidation
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• fasted mice exhibit higher long-chain 3-hydroxy-acylcarnitine species in the blood
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• female mice exhibit slightly lower serum glucose than wild-type mice after 6 hours of fasting
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• total blood ketone concentrations are lower during fasting
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• male mice exhibit higher respiratory exchange ratio (RER) than wild-type mice during the dark period when mice are most active, suggesting increased glucose metabolism and decreased fat oxidation
• mice exhibit higher VCO2 during dark hours while VO2 is not different
• respiratory exchange ratio is not different in females
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muscle
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• eccentric hypertrophy with a dilated cardiomyopathy
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• 12- to 15-month old mice show lower ejection fraction
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pigmentation
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• retinal pigment epithelium (RPE) degeneration as indicated by white or hypopigmented spots on fundus images
• 53% of eyes have hypopigmented areas present and retinal cross sections show 80% RPE disruption compared to 40% in wild-type mice
• RPE disruption is not due to lipid deposits
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vision/eye
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• retinal pigment epithelium (RPE) degeneration as indicated by white or hypopigmented spots on fundus images
• 53% of eyes have hypopigmented areas present and retinal cross sections show 80% RPE disruption compared to 40% in wild-type mice
• RPE disruption is not due to lipid deposits
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• 52% reduction in photopic b-wave amplitude indicating disrupted cone-mediated function
• however, scotopic b-wave amplitudes are not different
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• scotopic c-waves are reduced by 32%, indicating retinal pigment epithelium dysfunction
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• mice exhibit lower spatial frequency thresholds
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cellular
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• liver and cardiac palmitate oxidation is approximately 60% of wild-type suggesting reduced, but not absent, fatty acid oxidation
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