Analysis Tools
mortality/aging
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• homozygotes generally die between 2 and 5 months of age from rare irreversible seizures
• only 50% of homozygotes survive to 10 months of age
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behavior/neurological
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• in response to repeated i.p. injections of metrazol (an epileptogenic GABAA receptor antagonist), 12-week-old homozygotes show a normal initial response ("first twitch" phase) but progress significantly faster to the next two phases (tonic-clonic phase and tonic extension and death phase, respectively) than wild-type mice
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• at 5-7 months of age, homozygotes display longer escape latencies to locate a visible platform over the course of 4 days in the Morris water maze test
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• in the fear conditioning task, 5- to 7-month-old homozygotes exhibit significantly less freezing behavior than wild-type mice in both the context test and the auditory cue test
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• at 5-7 months of age, homozygotes display severe learning deficits in the Morris water maze hidden platform task
• in a transfer test in which the hidden platform is removed following training, mutants display a significantly lower number of crossings over the original platform location and spend significantly less time in the target quadrant than wild-type mice
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• homozygotes exhibit rare spontaneous seizures that reach a tonic extension and fail to resolve
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nervous system
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• in response to repeated i.p. injections of metrazol (an epileptogenic GABAA receptor antagonist), 12-week-old homozygotes show a normal initial response ("first twitch" phase) but progress significantly faster to the next two phases (tonic-clonic phase and tonic extension and death phase, respectively) than wild-type mice
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• homozygotes exhibit rare spontaneous seizures that reach a tonic extension and fail to resolve
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• after synapse stimulation, synapses of cultured cortical neurons obtained from mutant mice display defects in synaptic vesicle recycling, including a 25-30% smaller recycling vesicle pool size, slower destaining kinetics, and delayed vesicle repriming in mutant nerve terminals
• however, the ultrastructure of the synapse (including the total number of synaptic vesicles per synapse) is unaffected and no accumulation of endoyctic intermediates is observed, indicating that synaptic vesicle endocytosis is largely normal
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reproductive system
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• mutant spermatids are absent at stage IX and X
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• the number of membrane invaginations of tubulobulbar complexes formed at the apical cytoplasm of mutant Sertoli cells is ~50% of that in wild-type Sertoli cells
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• in mutant males, the ratio of stage VIII (defined as the stage with the latest spermatids) and stage IX (the stage immediately after spermatid release) is significantly higher and lower than that in wild-type mice, respectively
• no significant differences are observed in other spermatogenic stages
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• at stage VIII, the number of unreleased spermatids in mutant testes is ~2-fold higher than that in wild-type testes, indicating that spermatid release and the following transition from stage VIII to IX is prolonged
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endocrine/exocrine glands
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• the number of membrane invaginations of tubulobulbar complexes formed at the apical cytoplasm of mutant Sertoli cells is ~50% of that in wild-type Sertoli cells
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cellular
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• mutant spermatids are absent at stage IX and X
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