Phenotypes Associated with This Genotype

Genotype
MGI:5691569

• Allelic Composition: Pacsin1^tm1.1Bqu/Pacsin1^tm1.1Bqu
• Genetic Background: Not Specified

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

mortality/aging ( J:180017 )

N • homozygotes are born at normal Mendelian frequencies and survive for at least >1 year

growth/size/body

decreased body weight ( J:180017 )

• at 3-8 weeks of age, both female and male mice show a significant (~10%) reduction in body weight relative to wild-type controls

behavior/neurological

tonic-clonic seizures ( J:180017 )

• homozygotes develop generalized seizures with tonic-clonic convulsions without loss of consciousness in novelty situations

• a typical sequence consists of three phases: partial seizures, tonic-clonic convulsions and very quite pausing

• seizure probabilities rise to 50% and 80% at 18 and 23 weeks of age, respectively

nervous system

tonic-clonic seizures ( J:180017 )

• homozygotes develop generalized seizures with tonic-clonic convulsions without loss of consciousness in novelty situations

• a typical sequence consists of three phases: partial seizures, tonic-clonic convulsions and very quite pausing

• seizure probabilities rise to 50% and 80% at 18 and 23 weeks of age, respectively

increased hippocampus volume ( J:180017 )

• although gross hippocampal architecture is normal, hippocampal volume is increased by 7%

• however, no differences in brain weight, brain volume, brain histology or cortical thickness and layering are observed

• F-/G-actin ratios in the hippocampus and in resting synaptosomes remain normal

abnormal synapse morphology ( J:180017 )

• after prolonged light exposure, retinal rod ribbon synapses exhibit an increased frequency of clathrin labelling at the plasma membrane

abnormal synaptic vesicle morphology ( J:180017 )

• homozygotes show significantly increased SV diameters in hippocampal synapses and SV surfaces are less curved than wild-type; however, no differences in hippocampal synapse density, active zone length, SV density or number of docked SVs are observed

• after prolonged light exposure, retinal rod ribbon synapses exhibit significantly larger SV diameters

abnormal synaptic vesicle number ( J:180017 )

• after prolonged light exposure, retinal rod ribbon synapses exhibit a 58% reduction in SV density

abnormal nervous system electrophysiology ( J:180017 )

• homozygotes display altered hippocampal network activity upon stimulation

• after induction with kainic acid, the power of gamma frequency oscillations is increased by >230% in hippocampal slices relative to wild-type slices

• upon application of bicuculline (a GABAA receptor antagonist), the frequency of epileptiform discharges is increased by >3-fold relative to wild-type controls while the amplitudes of discharges rise by >90%

abnormal synaptic vesicle recycling ( J:180017 )

• FM1-43 dye recycling analysis in nerve terminals of cultured hippocampal neurons after moderate (300 APs at 10 Hz) and strong (800 APs at 80 Hz) stimulation revealed a trend towards reduced dye uptake after 300 stimuli (deltaF1) and significantly decreased dye uptake after 800 stimuli (deltaF2), suggesting defective activity-dependent SV endocytosis

• averaged deltaF2/deltaF1 ratio of individual nerve terminals is significantly reduced relative to wild-type neurons, suggesting impaired high-capacity retrieval of SVs

decreased excitatory postsynaptic current amplitude ( J:180017 )

• significant reduction in evoked EPSC (eEPSC) amplitudes upon an increasing strength of stimulation in CA1 pyramidal neurons

abnormal inhibitory postsynaptic currents ( J:180017 )

• significant reduction in eIPSC amplitudes upon an increasing strength of stimulation in CA1 pyramidal neurons

• reduction is apparently larger for the inhibitory (eIPSCs) than for the excitatory system (eEPSCs)

abnormal miniature excitatory postsynaptic currents ( J:180017 )

• whole-cell recordings from CA1 pyramidal neurons revealed significantly reduced frequencies of mEPSCs

• however, the peak amplitudes of mEPSCs are similar to those in wild-type neurons

decreased miniature inhibitory postsynaptic current frequency ( J:180017 )

• whole-cell recordings from CA1 pyramidal neurons revealed significantly reduced frequencies of mIPSCs

• however, the peak amplitudes of mIPSCs are similar to those in wild-type neurons

decreased synaptic depression ( J:180017 )

• short-term depression evoked by strong stimulations is significantly less pronounced in mutant hippocampal slices than in wild-type slices

cellular

abnormal vesicle-mediated transport ( J:180017 )

• homozygotes show defects in presynaptic membrane trafficking processes, especially under high-capacity retrieval conditions, accumulation of endocytic intermediates, impaired activity-dependent SV retrieval, and defective synaptic activity

• recruitment of dynamins I, II and III to the curved membranes of liposomes is impaired; recruitment defects can be completely rescued by addition of recombinant syndapin I to mutant brain cytosol

vision/eye

abnormal retina outer plexiform layer morphology ( J:180017 )

• homozygotes show severe alterations in rod photoreceptor ribbon synapses after light exposure

• after acute light exposure, rod ribbon synapses display a 110% increase in endosome-like structures as well as accumulations of branched tubular structures

• after prolonged light exposure, rod ribbon synapses show massive membrane trafficking defects with numerous coated omega-shaped profiles at the presynaptic plasma membrane, in addition to branched tubular structures and a 170% increase in endosome-like structures

• after prolonged light exposure, SV sizes are shifted to larger SV diameters, and SV density is reduced by 58%

reproductive system

reduced fertility ( J:180017 )

• fertility is reduced by ~30%