Analysis Tools
hearing/vestibular/ear
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• at >1 year, OHCs and IHCs are either both present or both absent in most sections of the organ of Corti
• a few cases where OHCs have degenerated while IHCs are still present are also observed
• the temporal relationship between the degeneration of fibrocytes and hair cells is variable
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• at 3 months, 2 of 4 (50%) homozygotes display degeneration of the organ of Corti
• at 5 months or later, 12 of 15 (80%) homozygotes display degeneration of the organ of Corti
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• at 5 months or later, homozygotes often show a significant loss of spiral ligament type I fibrocytes
• in contrast, spiral ligament type II fibrocytes are often preserved
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• at 5 months or later, homozygotes often show a significant loss of spiral ligament type III fibrocytes
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• however, young (<75 days) and old (>110 days) homozygotes show no significant differences in their endocochlear potential or K+ concentration in the scala media relative to age-matched wild-type mice
• old (but not young) homozygotes exhibit a significant decrease in the post-mortem (passive) endocochlear steady-state potential (SSP) relative to wild-type mice
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• homozygotes display a slowly progressive hearing loss over the first year of life, as shown by reduced thresholds of auditory brainstem responses to clicks as a function of age
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nervous system
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• upon exposure to flurothyl, 3-month-old homozygotes show reduced seizure thresholds and increased aberrant electrical activity, including spontaneous high-voltage spike-and-wave-like complexes, on electrocorticograms
• however, no spontaneous seizures are observed
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• at P13 (but not at P1), homozygotes exhibit severe degeneration of the cerebellum
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• at >1 year, homozygotes display degeneration of the cochlear ganglion, probably secondary to loss of cochlear hair cells
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• at P13 (but not at P1), homozygotes display severe degeneration of the sciatic nerve
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• at P13 (but not at P1), homozygotes display degeneration of the spinal cord
• analysis of ventral and dorsal roots of the spinal cord indicates that both motor and sensory nerves are affected
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• homozygotes exhibit progressive neurodegeneration in the PNS and CNS, esp. in the white matter
• at P13 (but not at P1), homozygotes exhibit severe degeneration of the sciatic nerve, spinal cord, hippocampus, cerebellum, and optic stalk while the corpus callosum remains unaffected
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• at >1 year, OHCs and IHCs are either both present or both absent in most sections of the organ of Corti
• a few cases where OHCs have degenerated while IHCs are still present are also observed
• the temporal relationship between the degeneration of fibrocytes and hair cells is variable
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• at P13 (but not at P1), homozygotes display severe hippocampal neurodegeneration, esp. in the outer molecular layer of the dentate gyrus along the hippocampal fissure
• vacuolization is more severe at 3 months of age than at P13
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• at 3 months, homozygotes exhibit swollen myelinated and unmyelinated axons in their degenerating hippocampi
• degenerating hippocampal unmyelinated axons have synapses that terminate on morphologically intact spines, suggesting that synaptic connections are established prior to degeneration
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behavior/neurological
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• upon exposure to flurothyl, 3-month-old homozygotes show reduced seizure thresholds and increased aberrant electrical activity, including spontaneous high-voltage spike-and-wave-like complexes, on electrocorticograms
• however, no spontaneous seizures are observed
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limb grasping
(
J:86183
)
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• when lifted by the tail, 3-week-old homozygotes display abnormal hindlimb grasping instead of the normal extension response
• at >1 year, abnormal forelimb grasping is also observed
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• at >1 year, homozygotes sometimes exhibit grossly abnormal positions of their hindlegs while sitting
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limp posture
(
J:86183
)
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• at >1 year, homozygotes sometimes lay flat on the ground
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cardiovascular system
hypertension
(
J:86183
)
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• at 3-5 months, homozygotes exhibit increased arterial hypertension relative to wild-type littermates (118 2 mmHg vs 100 2 mmHg, respectively)
• however, no difference in heart rates are observed
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muscle
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• at >1 year, homozygotes display an abnormal posture reminiscent of spasticity
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vision/eye
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• at P13 (but not at P1, homozygotes display degeneration of the optic stalk
• however, no retinal degeneration is observed
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cellular
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• homozygotes exhibit a severely impaired cell volume regulation, as assessed in proximal renal tubules and hippocampal neurons, and a moderately raised intraneuronal Cl- concentration relative to wild-type mice
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skeleton
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• at 5 months or later, homozygotes often show a significant loss of spiral ligament type I fibrocytes
• in contrast, spiral ligament type II fibrocytes are often preserved
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• at 5 months or later, homozygotes often show a significant loss of spiral ligament type III fibrocytes
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| agenesis of the corpus callosum with peripheral neuropathy | DOID:0090003 |
OMIM:218000 |
J:86183 | |
