Analysis Tools
mortality/aging
|
• mutants fail to thrive and die within 2 weeks of birth
|
nervous system
|
• accumulation of clathrin coats in neurons is observed
|
|
• 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
|
|
• 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
|
|
• 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
|
|
• synaptic transmission fails at earlier times at mutant synapses relative to controls
|
|
• IPSCs recover within 100 seconds to 46% of initial response in control cultures, but only to 11% in Dnm1-deficient neuronal cultures
• 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
|
|
• mEPSPs of cultured 10-15 day-old cortical neurons are significantly increased
|
behavior/neurological
|
• reduction in milk ingestion is apparent within several hours of birth
|
|
• poor motor coordination in animals becomes apparent in days following birth
|
