Analysis Tools
mortality/aging
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• preliminary observations on mice kept >5 months suggest that male mice survive ~6 months while female mice survive several months longer
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muscle
growth/size/body
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• increased heart weight at 2 months, but not at 5 months of age
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• mice are visibly smaller than wild-type at 8 weeks of age
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• both female and male mice show decreased body weight starting at 6-8 weeks of age
• total body weight remains significantly lower than that in wild-type controls at 5 months of age
• however, gain weight is normal until 6 weeks of age
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weight loss
(
J:294620
)
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• weight loss occurs in a linear pattern during week 7 and 8 but after 10 weeks of age body weight is shown to level out
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• increased kidney weight at 2 months, but not at 5 months of age
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• increased liver weight at 2 months, but not at 5 months of age
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adipose tissue
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• at 2 months of age, the subcutaneous fat layer is undetectable, indicating altered lipid metabolism
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• mice show decreased adipose tissue at 8 weeks of age
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integument
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• at 2 months of age, the subcutaneous fat layer is undetectable, indicating altered lipid metabolism
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• a change of fur color from black to blueish grey is first evident in the back area at 16 weeks of age
• the entire fur color changes from black to blueish grey by 20 weeks of age
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liver/biliary system
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• increased liver weight at 2 months, but not at 5 months of age
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• at 2 months of age, liver tissue morphology is abnormal with mild anisokaryosis, karyomegaly and occasional binucleated hepatocytes
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• mild increase in hepatocyte karyomegaly at 2 months of age
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• at 5 months of age, mice exhibit lipofuscin accumulation in the liver; the spot number and average area of lipofuscin are increased by approximately 3- and 3.5-fold, respectively, suggesting increased oxidative stress and liver damage
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• increased number of Ki-67-positive (proliferating) hepatocytes at 2 months of age
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• signs of hepatocyte regeneration with an increased number of proliferating cells, as shown by Ki-67 staining
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cellular
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• mild increase in hepatocyte karyomegaly at 2 months of age
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• mtDNA copy number is decreased in the liver, brain, heart, and skeletal muscle at both 2 and 5 months of age
• liver is the most severely affected organ with less than 2% of wild-type mtDNA content
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• at 2 months of age, mitochondrial cristae are disrupted in liver cells
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• at 2 months of age, round mitochondria are observed in liver cells
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• at 2 months of age, TEM analysis revealed swollen mitochondria with disrupted cristae in liver cells; areas occupied by mitochondria in liver cells are much larger than in wild-type cells
• however, cardiac mitochondria appear normal
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• increased number of Ki-67-positive (proliferating) hepatocytes at 2 months of age
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• at 2 months of age, protein levels of COXI (mt-encoded cytochrome c oxidase I) are decreased by 90% in the liver and by 20% in the skeletal muscle, with no apparent change seen in brain
• protein levels of ND1 (mt-encoded NADH dehydrogenase 1) are absent in the liver
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• at 2 months of age, no ND1 protein is detectable in the liver
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• at 5 months of age, mice exhibit lipofuscin accumulation in the liver; the spot number and average area of lipofuscin are increased by approximately 3- and 3.5-fold, respectively, suggesting increased oxidative stress and liver damage
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homeostasis/metabolism
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• serum glucose concentration is decreased by 70% at 2 months of age
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• 4-fold increase in serum cholesterol level at 2 months of age
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• 6-fold increase in serum alanine transaminase (ALT) level at 2 months of age
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• >3-fold increase in serum aspartate transaminase (AST) level at 2 months of age
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• serum albumin concentration is decreased by 34% at 2 months of age
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• microarray data analysis indicates increased lipid catabolism in liver tissue
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cardiovascular system
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• increased heart weight at 2 months, but not at 5 months of age
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renal/urinary system
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• increased kidney weight at 2 months, but not at 5 months of age
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pigmentation
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• a change of fur color from black to blueish grey is first evident in the back area at 16 weeks of age
• the entire fur color changes from black to blueish grey by 20 weeks of age
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behavior/neurological
| N |
• mice behave and move normally with no visible neurological signs at 5 months of age
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