Analysis Tools
behavior/neurological
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• body tremors are observed at ~2 wks of age and persist for several weeks, myelination abnormalities are not detected during period of tremors
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• on a rotarod test, mutants stay on the rod for a shorter period of time than wild-type mice and become progressively impaired with age
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• hindlimb weakness, unable to grip horizontal bar
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cellular
azoospermia
(
J:59025
)
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endocrine/exocrine glands
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• no indication of orchiditis, an autoimmune response against germ cells
• narrow tubules with poorly defined lumina containing aggregates of nucleated cells
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• lacking tight junctions forming the blood-testis barrier
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small testis
(
J:59025
)
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• testes are 30-50% smaller than in wild-type
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reproductive system
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• narrow tubules with poorly defined lumina containing aggregates of nucleated cells
• no indication of orchiditis, an autoimmune response against germ cells
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• lacking tight junctions forming the blood-testis barrier
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small testis
(
J:59025
)
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• testes are 30-50% smaller than in wild-type
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• no spermatozoa observed in seminiferous tubules, putatively due to disruption of blood-testis barrier
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azoospermia
(
J:59025
)
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nervous system
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• no observed neuronal loss or axonal degeneration in spinal cord, normal myelin thickness in dorsal and ventral white matter
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• at P90, homozygotes exhibit only minimal OHC loss in basal and apical cochlear turns (<20% in two animals); however, OHC loss is unlikely to account for increased ABR thresholds
• no IHC or spiral ganglion degeneration is observed
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• absence of intramyelinic tight junctions in optic nerve and spinal cord, radial components are absent in myelin of optic nerve and spinal cord
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hearing/vestibular/ear
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• at P90, homozygotes exhibit only minimal OHC loss in basal and apical cochlear turns (<20% in two animals); however, OHC loss is unlikely to account for increased ABR thresholds
• no IHC or spiral ganglion degeneration is observed
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• at 3 months, homozygotes lack TJ strands (i.e. intramembranous fibrils) in the basal cell layer of the stria vascularis; in contrast, strial marginal cell TJs and endothelial cell TJs remain intact
• gap junctions are present, forming large domains with defined borders in closely apposed basal cell membranes
• intermingling of gap junctions and TJs is also noted in basal cell membranes at P30, shortly after the onset of auditory function
• despite the close apposition of mutant basal cells, the diffusion barrier function of TJs is absent and paracellular diffusion of macromolecules into the stria vascularis is observed
• absence of basal cell TJs causes no major disruption to ion homeostasis, as endolymph K+ levels remain normal
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• adult homozygotes display EPs of ~29 mV relative to ~89 mV detected in wild-type mice
• total electrical potential is ~160 mV in wild-type mice (90 mV derived from the EP and assuming a hair cell resting potential of -70 mV) and 100 mV in homozygotes
• a 63% reduction causes a 50 dB SPL increase in hearing threshold, which represents a greater than 250-fold decrease in hearing sensitivity
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• ABRs from 32 kHz pure-tone stimuli are similar to those of wild-type littermates in terms of peak resolution and latencies for peaks I-III at 80 dB SPL
• however, peak amplitudes are reduced several-fold
• in addition, the latency for Peak V from homozygotes is longer than that from wild-type littermates
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• at 3 months, auditory brainstem response measurements indicate that hearing thresholds are elevated between 46.6 and 50.5 dB SPL across the frequency spectrum
• the hearing threshold is significantly increased (~80 dB SPL)
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• at P80-P90, wild-type mice are relatively insensitive to stimuli below ~4 kHz, but DPOAEs rise sharply above this frequency and remain significantly above the noise floor up to 16 kHz; in contrast, mutant DPOAEs show an attenuation >30 dB near f2 = 14 kHz
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• adult homozygotes exhibit severe deafness associated with a low endocochlear potential
• however, no major degenerative changes are noted in the cochlea
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vision/eye
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• impaired nerve conduction, determined by increased latency of visual evoked potential
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