Analysis Tools
mortality/aging
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• rarely do mutant mice live beyond 28 days of age
|
cellular
growth/size/body
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• noticeable by 12-14 days of age
(J:24235)
• by 10 days of age
(J:236593)
|
behavior/neurological
|
• homozygotes fail to acquire the normal righting reflex that wildtype siblings have at 10 days of age
|
hyperactivity
(
J:24235
)
|
• noticeable by 12-14 days of age
• is not accompanied by tremor
|
|
• sudden sounds stimulate bursts of activity
|
nervous system
| N |
• the number and distribution of oligodendrocytes in the spinal cord and brain appears normal, electron microscopy of semithin sections at 16 days of age fails to detect any abnormal myelination in the optic nerve, cerebellum, or spinal cord, and myelin appears normal at the ultrastructural level in spinal cord and optic nerve
(J:43719)
• Granule, stellate, basket, golgi, Lugaro and unipolar brush border cells appear normal and correctly positioned
(J:236593)
|
|
• homomzygotes have a proximal retraction of the climbing fiber domain with climbing fiber terminals encompassing only 68.9% of the molecular layer instead of 83.3% in controls, but this altered climbing fiber-Purkinje cell innervation does not alter the amplitude of excitatory postsynaptic currents in whole-cell patchclamping
|
|
• aberrant Purkinje cell morphology is found throughout all lobules and across the vermis, with Purkinje cells having mitochondrial clumping, endoplasmic reticulum vesiculation, increased electron density of the cytoplasm, increased numbers of multivesicular endosomes, lysosomes, and double-membrane bound autophagosomes-like and autolysosome-like bodies
|
|
• evident by 18 days of age, primarily in the anterior lobe and the banks of the secondary fissure, with damage in all compartments of the Purkinje neuron, although no vacuoles are observed in the Purkinje cell layer between 16 and 21 days of age, and no Purkinje cell degeneration was found in the inferior olivary complex
|
|
• torpedoes and spheroids containing autophagosome-like and autolysosome-like bodies and swollen endoplasmic reticulum are found in the Purkinje axons in the folial white matter and cerebellar and vestivular neuclei, and the dystrophic terminals contain enlarged mitochondria, lysosomes, dilated cisterns of the smooth endoplasmic reticulum and clustered synaptic vesicles
|
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• cerebellar and vestibular nuclei have many dystrophic axons
|
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• most Purkinje cells have malformed dendritic branching, some with no clear secondary or tertiary dendritic branches, many spiny branchlets emerging directly from the primary dendrite, there is a loss of parasagittal planarity with dendritic branches showing meandering arbors which overlap in coverage and malformed dendritic spines with thin, elongaged filopodia
|
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• although the foliation and tri-laminar organization of the cerebellum appear generally normal, the cerebellum is disproportionately small
|
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• occasional degenerating axons are observed in P16 optic nerve
|
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• immunohistochemistry found no loss of parallel fiber terminals, and miniature excitatory postsynaptic currents from parasagittal cerebellar slices show an average frequency comparable to controls, but the amplitude is decreased to an average of 6.04 in homozygotes compared with 7.92 in controls
|
vision/eye
|
• occasional degenerating axons are observed in P16 optic nerve
|
