Analysis Tools
mortality/aging
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• mutants fail to thrive and die within 2 weeks of birth
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nervous system
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• accumulation of clathrin coats in neurons is observed
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• in cultured cortical neurons, vesicles have a heterogeneous and generally slightly larger size in mutant synapses
• at synapses in mutant not control neuronal cultures, clathrin-coated vesicular profiles, many of which are interconnected, are common; in many synapses, these structures are buds connected to the plasma membrane by narrow tubules, indicating that fission of clathrin-coated vesicles is impaired
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• cultured cortical neurons (21 days of age in vitro) show a reduction of ~20% in synaptic vesicle numbers
• total number of synaptic vesicles in cultured neurons after receiving a 90 second stimulus is steeply reduced relative to control cultures
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• after 90 second stimulation, recycling is impaired with recovery lagging behind control neuronal cultures, but resumes efficiently upon cessation of stimulation
• at higher stimulation frequencies, synaptic vesicle endocytosis is unable to compensate for exocytosis (determined by endocytic/exocytic ratio) in mutant neuronal cultures compared to wild-type cultures
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• synaptic transmission fails at earlier times at mutant synapses relative to controls
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• miniature IPSCs (mIPSCs) are increased
• IPSCs elicited by single presynaptic stimuli of cultured 10-15 day old cortical neurons show significant reduction in peak amplitude
• during trains of 1000 stimuli, peak amplitudes of IPSCs from cultured neurons tend to depress faster than wild-type
• IPSCs recover within 100 seconds to 46% of initial response in control cultures, but only to 11% in Dnm1-deficient neuronal cultures
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• mEPSPs of cultured 10-15 day-old cortical neurons are significantly increased
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behavior/neurological
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• reduction in milk ingestion is apparent within several hours of birth
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• poor motor coordination in animals becomes apparent in days following birth
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