Analysis Tools
mortality/aging
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• mice exhibit moderately reduced viability at weaning; cause is not determined but may be related to seizures
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behavior/neurological
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• grip strength is significantly reduced at 5 and 11 weeks of age
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• approximately half of mice exhibit severe handling-associated seizures between 3 and 12 months of age
• however, no histologic lesions are detected in brain
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adipose tissue
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• mice exhibit a striking increase in normalized body fat percentage on both a normal chow and a high-fat diet
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growth/size/body
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• chow-fed mice show significantly decreased lean body mass relative to diet-matched controls
• however, both male and female mice exhibit normal body weights
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muscle
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• in the 14- week-old hindlimb, marked replacement of myocytes by adipocytes is noted in the vastus lateralis and tensor fascia latae muscles, whereas adipocytes are relatively uncommon in other proximal leg muscles
• adipocytes in the rectus femoris muscle appear in clusters
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• at 14 weeks of age, less severely affected atrophic fibers exhibit disordered myofibril alignment and disrupted banding patterns; numerous type II myocytes show loss of normal myosin banding pattern
• fast-twitch (type II) fibers are more susceptible to degeneration and transdifferentiation into adipose tissue than slow-twitch (type I) fibers
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• at 14 weeks of age, some degenerating skeletal muscle fibers progress to necrosis with disrupted flocculated sarcoplasm and occasional intracellular macrophages; both heavy chain myosin and desmin are typically absent in necrotic myocytes
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• at 14 weeks of age, the majority of skeletal myocytes have centralized nuclei
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• at 14 weeks of age, many but not all muscle groups examined exhibit extensive mild degenerative changes: scattered individual and small groups of muscle fibers show features of degeneration, including internalized nuclei, hypereosinophilia (hyaline degeneration), and loss of cross-striations
• at early stages, individual hypereosinophilic degenerating fibers show extensive rearrangement and loss of normal banding patterns of both myosin and desmin
• by 37 weeks of age, severely affected muscles show scattered clusters of rounded atrophic fibers with centralized nuclei while degenerating myocytes are surrounded by abundant mature white adipocytes
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• mice develop severe sarcopenia
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• at 37 weeks of age, morphological signs of skeletal muscle regeneration (small-diameter regenerating fibers with rows of centralized MyoD/Myogenin-positive nuclei), are detected only in the diaphragm
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• at 5 and 11 weeks of age, almost all mice fall off the screen immediately in an inverted screen assay, indicating muscle weakness
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• mice develop degenerative myopathy with extensive replacement of skeletal myocytes by adipocytes
• at 14 weeks of age (early stages), the extent of myosteatosis is generally mild but varies among muscles
• by 37 weeks of age, the severity and extent of sarcopenia with intramuscular and interstitial steatosis is markedly increased
• myopathic lesions are restricted to type II (fast twitch) muscle fibers; mixed fiber type muscles (e.g., vastus intermedius and soleus) are largely spared
• however, only minimal inflammation, fibrosis, and muscle regeneration are observed
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cardiovascular system
| N |
• 14- and 37-week-old mice exhibit no histological evidence of steatosis or lipotoxicity in the heart
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• systolic blood pressure is significantly decreased at 12 weeks of age
• however, no notable lesions are detected in the heart
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cellular
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• at 14 weeks of age, some degenerating skeletal muscle fibers progress to necrosis with disrupted flocculated sarcoplasm and occasional intracellular macrophages; both heavy chain myosin and desmin are typically absent in necrotic myocytes
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• myopathy is associated with extensive transdifferentiation and replacement of muscle by well-differentiated adipose tissue
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homeostasis/metabolism
| N |
• 12-week-old mice show no differences in fed serum chemistry levels (including sodium, calcium, phosphate, glucose, creatinine, and total bilirubin levels) relative to wild-type controls; fasting serum glucose levels are also normal
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• serum ALT level is significantly increased at 12 weeks of age
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limbs/digits/tail
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• in the 14- week-old hindlimb, marked replacement of myocytes by adipocytes is noted in the vastus lateralis and tensor fascia latae muscles, whereas adipocytes are relatively uncommon in other proximal leg muscles
• adipocytes in the rectus femoris muscle appear in clusters
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nervous system
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• approximately half of mice exhibit severe handling-associated seizures between 3 and 12 months of age
• however, no histologic lesions are detected in brain
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liver/biliary system
| N |
• 14- and 37-week-old mice exhibit normal hepatocytes with no histologic evidence of lipidosis or lipotoxicity
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