Analysis Tools
mortality/aging
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• on an inbred FVB/NJ background, 40% of homozygotes die at an average age of about 2.2 months of unknown causes
• however, surviving homozygotes exhibit apparently normal life spans (greater than 10 months)
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behavior/neurological
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• at one month of age, homozygotes fall off an accelerating rotarod at significantly slower speeds relative to wild-type
• in addition, homozygotes perform poorly in the hanging wire assay
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abnormal gait
(
J:92539
)
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• homozygotes display an uneven gait pattern
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• homozygotes display a shorter stride length
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• 6% of homozygotes display spontaneous and persistent unidirectional circling
• however, no cerebellar, basal ganglia or vestibular lesions are observed at necropsy
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renal/urinary system
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• homozygotes exhibit a 4-fold increase in overall phasic contractile activity in urinary bladder smooth muscle (UBSM)
• homozygotes show a 3-fold increase in nerve-mediated contractility in UBSM
• homozygotes show absence of voltage- and calcium-activated large conductance potassium BK currents in UBSM
• in contrast, local calcium transients ("calcium sparks") and voltage-gated (IBTX-insensitive) potassium currents are unaffected
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• homozygotes display an increased urination frequency, with 8.8 times more small urine spots (<0.5 cm) in an hour than wild-type mice
• in addition, homozygotes exhibit yellow perineal staining, not observed in wild-type mice
• however, no significant differences in water intake or urine production are observed
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• homozygotes display bladder overactivity and urinary incontinence
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growth/size/body
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• at 2 weeks, homozygotes show a 27% reduction in body weight relative to wild-type mice
• however, a normal body weight is achieved after 5 weeks
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reproductive system
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• unexpectedly, homozygotes are able to produce offspring; however, the efficiency of successful matings is reduced, with only 1 of 20 male homozygotes (set up for mating to wild-type females) being able to sire a litter of normal size
• average litter size from heterozygous females mated to heterozygous males is 7.8 0.4 pups
• average litter size from homozygous females mated to heterozygous males is 3.9 0.5 pups
• however, homozygous females can carry litters to term and adequately feed and care for their pups
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hearing/vestibular/ear
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• at 3 weeks, mutant IHCs lack the fast activating BK potassium currents, with no compensatory changes in the remaining outward currents or in transcripts encoding ion channels or transporters
• despite the absence of the BK current or other fast activating current, mutant IHCs exhibit normal morphology and synaptic innervation at 8 weeks
• surprisingly, at 12 weeks, homozygotes show normal IHC function, with no significant differences in ABR thresholds for click or pure tone stimuli (8, 16, and 32 kHz) relative to wild-type mice, although first peak latencies are slightly delayed at both 1 kHz and 16 kHz
• in addition, at 12 weeks, homozygotes display an apparently normal OHC function, with no differecens in DPOAE magnitudes over a range of frequencies relative to wild-type mice
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• at 5 days after exposure to a 105-dB SPL sound stimulus for 1 hr, 8-wk-old homozygotes display significantly reduced ABR threshold shifts across most test frequencies relative to wild-type mice, indicating resistance to noise-induced hearing loss
• however, at 20 days after noise exposure, no consistent differences in IHC morphology or afferent innervation are noted between mutant and wild-type mice
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nervous system
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• at 3 weeks, mutant IHCs lack the fast activating BK potassium currents, with no compensatory changes in the remaining outward currents or in transcripts encoding ion channels or transporters
• despite the absence of the BK current or other fast activating current, mutant IHCs exhibit normal morphology and synaptic innervation at 8 weeks
• surprisingly, at 12 weeks, homozygotes show normal IHC function, with no significant differences in ABR thresholds for click or pure tone stimuli (8, 16, and 32 kHz) relative to wild-type mice, although first peak latencies are slightly delayed at both 1 kHz and 16 kHz
• in addition, at 12 weeks, homozygotes display an apparently normal OHC function, with no differecens in DPOAE magnitudes over a range of frequencies relative to wild-type mice
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