Analysis Tools
mortality/aging
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• all mice die by P40 or are euthanized by P35 due to paralysis and lack of response to stimuli
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growth/size/body
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• mice fail to gain weight past P18
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• mice develop normally until P18 but fail to thrive and subsequently are smaller than controls
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behavior/neurological
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• loss of balance and rolling after ~P25
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• mice exhibit significantly reduced grip strength at P22-P26 relative to controls
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• lack of response to stimuli by P35
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muscle
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• in the hind limb suspension test, neonates show reduced muscle strength performance, with a consistently shorter hang time and decreased number of pull attempts starting at P8 and continuing to P10
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immune system
cellular
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• mice exhibit an accumulation of structurally abnormal mitochondria in cerebellar granule cells that is associated with defective processing of OPA1, a key molecule for mitochondrial fusion and cristae remodeling, leading to depletion of the L-isoform
• abnormal OPA1 processing is brain-specific and can be detected at P25
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• mice show a significant increase in the number of TUNEL+ cells in discrete brain regions, i.e. striatum, cerebellum and entorhinal cortex, at P30 relative to controls
• cell death in the striatum and cerebellum is detectable by P25 and progressively worsens over time
• dying cells in the entorhinal cortex are seen at P30 but not at P25
• whereas cell death is widespread in the striatum, cerebellar cell death appears to be localized in the granule cell layer with a prominent amount of TUNEL+ cells
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• at P25, Complex I and Complex II enzyme levels are reduced in the cerebellar granule cell layer and in the striatum, but not in the cerebral cortex, relative to controls, suggesting that electron transport chain function is impaired
• reduction in the levels of respiratory enzymes is confined to the regions that undergo cell death
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hematopoietic system
endocrine/exocrine glands
nervous system
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• despite increased cerebellar cell death, P30-P35 cerebella appear grossly unaffected, with no signs of demyelination, and normal Purkinje cell organization, neuronal populations and granule cell layer morphology relative to wild-type controls
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• mice show a significant increase in the number of TUNEL+ cells in discrete brain regions, i.e. striatum, cerebellum and entorhinal cortex, at P30 relative to controls
• cell death in the striatum and cerebellum is detectable by P25 and progressively worsens over time
• dying cells in the entorhinal cortex are seen at P30 but not at P25
• whereas cell death is widespread in the striatum, cerebellar cell death appears to be localized in the granule cell layer with a prominent amount of TUNEL+ cells
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