homeostasis/metabolism
• impaired autophagic flux in the brain and spinal cord at 4 months
|
mortality/aging
• 50% of mice die by 16 weeks
• all mice die by 19 weeks
|
nervous system
N |
• mice do not exhibit accumulation of TDP-43 (Tardbp) aggregates in motor neurons
|
• massive
|
• neural abnormalities increase progressively with age
|
• thin white matter between the cortex and hippocampal pyramidal cells
|
• atrophic
|
• reduced ratio of cortical to dorsoventral thickness
|
• shrunken appearance
|
• with age
|
• reduced
|
• vacuolated cells in the cingulate cortex and to a lesser extent in other cortices, hippocampus, thalamus, and hypothalamus
• vacuolated cells in the white matter regions including the corpus callosum, the alveus of the hippocampus and the internal capsule
|
astrocytosis
(
J:193420
)
• in the cerebrum, cerebellum and spinal cord
|
• numerous vacuolated cells in the spinal cord gray and white matter
|
• irregularly arranged in the alveus of the hippocampus
|
• thinned and split in the deep cerebellar nuclei axons
|
• in cortical layers 1 through 4
• reduced interneuron numbers in the anterior horn of the lumbar spinal cord
• however, the number of motor neurons is normal
|
• in the fifth layers of the motor and sensory cortices
|
• in the cerebrum, cerebellum and spinal cord that increase in number and size with age
|
• massive
• of Purkinje cell axons
|
• of Purkinje cell axon terminals
|
• eosinophilic spheroids in the cortex
• large eosinophilic spheroids in the deep cerebellar nuclei
|
behavior/neurological
• motor and behavioral deficits beginning at 6 weeks and progressively worsening
|
• beginning at 6 weeks and progressively worsening
|
• hyperextended position of hind limbs
|
• in 8 of 12 mice at 6 weeks
• in all mice at 8 weeks
|
• at 3 months
|
growth/size/body
• by 3 months
|
• at 2 weeks
|
cellular
• impaired autophagic flux in the brain and spinal cord at 4 months
|
• massive
|