| Phenotypic Profile |
| Category |
Entity |
Quantity |
Experimental Paradigm |
Age at Testing |
| Motor phenotype |
Motor coordination and balance4 |
Increased
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, nine trials 4 to 40 rpm in 300 s
|
Accelerating rotarod test |
6 weeks |
| |
|
Description: Normal initial coordination with increased learning rate, compared to male littermate controls
Exp Paradigm: Accelerating rotarod, nine trials 4 to 40 rpm in 300 s |
|
|
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Synapse density: inhibitory1 |
Increased
Description: Increased density of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Immunohistochemistry; fluorescence microscopy
|
Immunohistochemistry |
3 months |
| |
|
Description: Increased density of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Immunohistochemistry; fluorescence microscopy |
|
|
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Neuronal number: enteric neurons5 |
Increased
Description: Mutants show increase in the number of myenteric neurons (hu cells) and increase in nnos positive inhibitory enteric neurons per ganglion in the proximal jejunum.
Exp Paradigm: Proximal jejunum
|
Immunofluorescence staining |
8-12 weeks |
| |
|
Description: Mutants show increase in the number of myenteric neurons (hu cells) and increase in nnos positive inhibitory enteric neurons per ganglion in the proximal jejunum.
Exp Paradigm: Proximal jejunum |
|
|
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Hippocampal morphology2 |
Increased
Description: Increased dendritic branching of pyramidal neurons in stratum radiatum, compared to wild type, but no change in stratum lacunosum or stratum moleculare
Exp Paradigm: Sholl analysis
|
Sholl analysis |
Unreported |
| |
|
Description: Increased dendritic branching of pyramidal neurons in stratum radiatum, compared to wild type, but no change in stratum lacunosum or stratum moleculare
Exp Paradigm: Sholl analysis |
|
|
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Synaptic morphology2 |
Decreased
Description: Decreased spine area, bouton area and number of vesicles per bouton, compared to wild type
Exp Paradigm: Electron microscopy analysis
|
Electron microscopy |
Unreported |
| |
|
Description: Decreased spine area, bouton area and number of vesicles per bouton, compared to wild type
Exp Paradigm: Electron microscopy analysis |
|
|
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents2 |
Increased
Description: Increased frequency of spontaneous mepscs in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased frequency of spontaneous mepscs in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings |
|
|
| Neurophysiology |
Synaptic transmission: excitatory2 |
Abnormal
Description: Increased sensitivity to ifenprodil, nr1/nr2b heterotetrameric-selective antagonist, compared to wild type
Exp Paradigm: Field potential recordings
|
Field potential recordings |
Unreported |
| |
|
Description: Increased sensitivity to ifenprodil, nr1/nr2b heterotetrameric-selective antagonist, compared to wild type
Exp Paradigm: Field potential recordings |
|
|
| Neurophysiology |
Neurotransmitter release3 |
Increased
Description: Increased gaba transient in synaptic cleft indicated by decreased reduction of mgpscs amplitude after bath application of tpmpa, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker
|
Whole-cell patch clamp |
P11-p15 |
| |
|
Description: Increased gaba transient in synaptic cleft indicated by decreased reduction of mgpscs amplitude after bath application of tpmpa, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker |
|
|
| Neurophysiology |
Spontaneous post synaptic events: inhibitory currents2 |
Increased
Description: Increased frequency of spontaneous mipscs in somatosensory cortex, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased frequency of spontaneous mipscs in somatosensory cortex, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings |
|
|
| Neurophysiology |
Synaptic transmission: inhibitory5 |
Decreased
Description: Mutants show decrease in enteric gabaergic neurotransmission measured by failure to extend colonic migrating motor complexes along the length of the colon in the presence of gaba-a receptor antagonists in acute ex vivo colons. mutants show no change in the number of cmmcs in the presence of gaba-a receptor antagonist cgp 54626 indicating the involvement of gaba-a receptor recific mechanism.
Exp Paradigm: Colons challenged by exposure to the gabaa receptor antagonists bicuculline or gabazine
|
Immunofluorescence staining |
8-12 weeks |
| |
|
Description: Mutants show decrease in enteric gabaergic neurotransmission measured by failure to extend colonic migrating motor complexes along the length of the colon in the presence of gaba-a receptor antagonists in acute ex vivo colons. mutants show no change in the number of cmmcs in the presence of gaba-a receptor antagonist cgp 54626 indicating the involvement of gaba-a receptor recific mechanism.
Exp Paradigm: Colons challenged by exposure to the gabaa receptor antagonists bicuculline or gabazine |
|
|
| Neurophysiology |
Spontaneous post synaptic events3 |
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
|
Whole-cell patch clamp |
P4-p9 |
| |
|
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings |
|
|
| Neurophysiology |
Synaptic transmission: excitatory2 |
Increased
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship)
|
Field potential recordings |
Unreported |
| |
|
Description: Increased fepsp, compared to wild type
Exp Paradigm: Field potential recordings: slope of epsp by range of stimulus (input/ output relationship) |
|
|
| Neurophysiology |
Neuronal ion channel activity2 |
Increased
Description: Increased decay time constant or nmdar-mediated response, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased decay time constant or nmdar-mediated response, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings |
|
|
| Neurophysiology |
Spontaneous post synaptic events: inhibitory currents1 |
Increased
Description: Increased frequency of spontaneous inhibitory mini events but no change in amplitude
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased frequency of spontaneous inhibitory mini events but no change in amplitude
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex |
|
|
| Neurophysiology |
Synaptic transmission: inhibitory1 |
Increased
Description: Increased amplitude of evoked inhibitory response
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased amplitude of evoked inhibitory response
Exp Paradigm: Whole cell patch-clamp recordings in layer 2-3 of somtosensory cortex |
|
|
| Neurophysiology |
Spontaneous post synaptic events3 |
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
|
Whole-cell patch clamp |
P11-p15 |
| |
|
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings |
|
|
| Neurophysiology |
Synaptic plasticity: hippocampal ltp2 |
Increased
Description: Increased fepsp slope 55-60 minutes after tetanic stimulation, compared to wild type
Exp Paradigm: Field potential recordings; long-term potentiation three 100-hz, 1-s stimuli
|
Field potential recordings |
Unreported |
| |
|
Description: Increased fepsp slope 55-60 minutes after tetanic stimulation, compared to wild type
Exp Paradigm: Field potential recordings; long-term potentiation three 100-hz, 1-s stimuli |
|
|
| Neurophysiology |
Intrinsic bursting events or spikes3 |
Increased
Description: Increased spontaneous giant depolarizing potentials indicated by shorter cumulative inter-event-interval and higher cumulative probability in ca3 region of hippocampus, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings from ca3 region of hippocampus
|
Whole-cell patch clamp |
P4-p9 |
| |
|
Description: Increased spontaneous giant depolarizing potentials indicated by shorter cumulative inter-event-interval and higher cumulative probability in ca3 region of hippocampus, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings from ca3 region of hippocampus |
|
|
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents3 |
Increased
Description: Increased frequency of spontaneous mini ampa postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
|
Whole-cell patch clamp |
4-5 weeks |
| |
|
Description: Increased frequency of spontaneous mini ampa postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings |
|
|
| Neurophysiology |
Synaptic transmission: inhibitory3 |
Abnormal
Description: Faster decay time of miniature gabaergic events, but no change in rise time, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker
|
Whole-cell patch clamp |
P9-p11 |
| |
|
Description: Faster decay time of miniature gabaergic events, but no change in rise time, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings of mgpscs with gabaa competitive blocker |
|
|
| Neurophysiology |
Spontaneous post synaptic events3 |
Increased
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings
|
Whole-cell patch clamp |
4-5 weeks |
| |
|
Description: Increased frequency of spontaneous mini gaba postsynaptic current events but no change in amplitude, compared to wild type
Exp Paradigm: Whole-cell voltage-clamp recordings |
|
|
| Neurophysiology |
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2 |
Increased
Description: Increased ratio of nmda/ampa-mediated transmission in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings
|
Whole-cell patch clamp |
Unreported |
| |
|
Description: Increased ratio of nmda/ampa-mediated transmission in hippocampus, compared to wild type
Exp Paradigm: Whole cell patch-clamp recordings |
|
|
| Social behavior |
Social memory2 |
Decreased
Description: Decreased preference for novel social target, compared to wild type
Exp Paradigm: Three-chamber social approach test: social novelty
|
Three-chamber social approach test |
Unreported |
| |
|
Description: Decreased preference for novel social target, compared to wild type
Exp Paradigm: Three-chamber social approach test: social novelty |
|
|
| Social behavior |
Social interaction1 |
Decreased
Description: Reduced social approach and preference for social interaction
Exp Paradigm: Social interaction
|
Reciprocal social interaction test |
2-4 months |
| |
|
Description: Reduced social approach and preference for social interaction
Exp Paradigm: Social interaction |
|
|
| Social behavior |
Social interaction2 |
Decreased
Description: Decreased exploration of social target, compared to wild type
Exp Paradigm: Caged adult social interaction test
|
Reciprocal social interaction test |
Unreported |
| |
|
Description: Decreased exploration of social target, compared to wild type
Exp Paradigm: Caged adult social interaction test |
|
|
| Physiological parameters |
Metabolic function5 |
Abnormal
Description: Mutant fecal microbiota show difference in the carbon utilization of the fecal microbial communities. mutants show no change in microbial functional richness in fecal samples, measured as the number of different carbon sources the community could utilize. mutant fecal microbiota show higher utilization of glucosaminic acid compared with controls at 9weeks. mutant fecal microbiota show no change in the utilization of amide/amine at 9weeks. mutant fecal microbiota show marginal decrease in the utilization of carbohydrate i-erythritol at 9 weeks. mutant fecal microbiota show no change in the utilization of amino acid t-phenylalanine compare with controls at 9 weeks. mutants show no change in overall metabolic profiles.
Exp Paradigm: Carbon substrate utiliztion assay
|
Spectrophotometry |
5-9 weeks |
| Physiological parameters |
Intestinal microbiota functional profile5 |
Abnormal
Description: Abnormal carbon substrate utilization of microbial communities
Exp Paradigm: NA
|
Carbon substrate utilization assay |
5-9 weeks |
| |
|
Description: Abnormal carbon substrate utilization of microbial communities
Exp Paradigm: NA |
|
|
| Physiological parameters |
Intestinal microbiota composition5 |
Abnormal
Description: Abnormal structure of the fecal microbial community; cage environment and age contributed to microbial profiles; no change in microbial richness; no change in overall abundance of different bacterial phyla at 5 and 9 weeks; firmicutes and bacteroidetes (93%); proteobacteria (3%) and actinobacteria, candidate, cyanobacteria, and tenericutes (4%); no change in microbial diversity at 9 weeks but difference in the abundance of 6 otus
Exp Paradigm: NA
|
16s rrna gene sequence analysis for identification of bacteria |
5-9 weeks |
| |
|
Description: Abnormal structure of the fecal microbial community; cage environment and age contributed to microbial profiles; no change in microbial richness; no change in overall abundance of different bacterial phyla at 5 and 9 weeks; firmicutes and bacteroidetes (93%); proteobacteria (3%) and actinobacteria, candidate, cyanobacteria, and tenericutes (4%); no change in microbial diversity at 9 weeks but difference in the abundance of 6 otus
Exp Paradigm: NA |
|
|
| Physiological parameters |
Digestive system function: gastrointestinal motility5 |
Increased
Description: Mutants show faster small intestine transit compared with controls. mutants show a higher ratio of dye front to the length of the small intestine compared with controls.
Exp Paradigm: Orally gavaged carmine red dye front was measured.
|
Intestinal transit time |
Adult |
| |
|
Description: Mutants show faster small intestine transit compared with controls. mutants show a higher ratio of dye front to the length of the small intestine compared with controls.
Exp Paradigm: Orally gavaged carmine red dye front was measured. |
|
|
| Learning & memory |
Spatial learning1 |
Increased
Description: Enhanced spatial learning
Exp Paradigm: Morris water maze test
|
Morris water maze test |
2-4 months |
| |
|
Description: Enhanced spatial learning
Exp Paradigm: Morris water maze test |
|
|
| Molecular profile |
Protein expression level evidence1 |
Decreased
Description: Decreased expression of nl1 protein
Exp Paradigm: Western blot
|
Western blot |
3 months |
| |
|
Description: Decreased expression of nl1 protein
Exp Paradigm: Western blot |
|
|
| Molecular profile |
Protein expression level evidence2 |
Increased
Description: Increased level of excitatory postsynaptic scaffolding proteins psd95, sap102, compared to wild type
Exp Paradigm: Western blot
|
Western blot |
Unreported |
| |
|
Description: Increased level of excitatory postsynaptic scaffolding proteins psd95, sap102, compared to wild type
Exp Paradigm: Western blot |
|
|
| Molecular profile |
Targeted expression5 |
Decreased
Description: Mutants express the mutant allele and not the wildtype allele as expressed in controls.
Exp Paradigm: Ileum
|
Quantitative pcr (qrt-pcr) |
8 weeks |
| |
|
Description: Mutants express the mutant allele and not the wildtype allele as expressed in controls.
Exp Paradigm: Ileum |
|
|
| Molecular profile |
Protein expression level evidence1 |
Increased
Description: Increased expression of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Western blot
|
Western blot |
3 months |
| |
|
Description: Increased expression of inhibitory synapse protein markers: vgat and gephyrin
Exp Paradigm: Western blot |
|
|
| Molecular profile |
Targeted expression1 |
Decreased
Description: Decreased expression of nl3 protein
Exp Paradigm: Western blot
|
Western blot |
3 months |
| |
|
Description: Decreased expression of nl3 protein
Exp Paradigm: Western blot |
|
|
| Molecular profile |
Protein expression level evidence2 |
Increased
Description: Increase level of nr2b, nr2a subunits, compared to wild type
Exp Paradigm: Western blot
|
Western blot |
Unreported |
| |
|
Description: Increase level of nr2b, nr2a subunits, compared to wild type
Exp Paradigm: Western blot |
|
|
| Molecular profile |
Targeted expression2 |
Decreased
Description: Decrease in level of nl3, compared to wild type, compared to wild type
Exp Paradigm: Western blot
|
Western blot |
Unreported |
| |
|
Description: Decrease in level of nl3, compared to wild type, compared to wild type
Exp Paradigm: Western blot |
|
|
| Developmental profile |
Digestive system development5 |
No change |
Gross necroscopy |
8-12 weeks |
| Developmental profile |
Size/growth5 |
No change |
Body weight measurement |
8-12 weeks |
| Developmental profile |
Tissue weight5 |
No change |
Measurement of tissue weight |
8-12 weeks |
| Emotion |
Anxiety1 |
No change |
Elevated plus maze test |
2-4 months |
| Emotion |
Anxiety1 |
No change |
Open field test |
2-4 months |
| Emotion |
Exploratory activity1 |
No change |
Novel object recognition test |
2-4 months |
| Molecular profile |
Gene expression1 |
No change |
Quantitative pcr (qrt-pcr) |
3 months |
| Molecular profile |
Protein expression level evidence2 |
No change |
Western blot |
Unreported |
| Molecular profile |
Protein expression level evidence2 |
No change |
Western blot |
Unreported |
| Molecular profile |
Protein expression level evidence3 |
No change |
Peak-scaled non-stationary fluctuation analysis |
Unreported |
| Molecular profile |
Protein expression level evidence1 |
No change |
Western blot |
3 months |
| Motor phenotype |
General locomotor activity1 |
No change |
Light-dark exploration test |
2-4 months |
| Motor phenotype |
Motor coordination and balance1 |
No change |
Accelerating rotarod test |
2-4 months |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Brain morphology1 |
No change |
Immunohistochemistry |
3 months |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Brain morphology1 |
No change |
Electron microscopy |
8 weeks |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Neuronal number: enteric neurons5 |
No change |
Immunofluorescence staining |
8-12 weeks |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Neuronal number: enteric neurons: gabaergic5 |
No change |
Immunofluorescence staining |
8-12 weeks |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Synapse density2 |
No change |
Fluorescence microscopy |
Unreported |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Synapse density: excitatory1 |
No change |
Immunohistochemistry |
3 months |
| Neuroanatomy / Ultrastructure / Cytoarchitecture |
Synaptic morphology2 |
No change |
Electron microscopy |
Unreported |
| Neurophysiology |
Membrane potential3 |
No change |
Whole-cell patch clamp |
P4-p9 |
| Neurophysiology |
Neuronal ion channel activity3 |
No change |
Whole-cell patch clamp |
P11-p15 |
| Neurophysiology |
Neurotransporter activity3 |
No change |
Whole-cell patch clamp |
P11-p16 |
| Neurophysiology |
Presynaptic function: paired-pulse facilitation2 |
No change |
Field potential recordings |
Unreported |
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents2 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents1 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents3 |
No change |
Whole-cell patch clamp |
P11-p15 |
| Neurophysiology |
Spontaneous post synaptic events: excitatory currents3 |
No change |
Whole-cell patch clamp |
P4-p9 |
| Neurophysiology |
Spontaneous post synaptic events: inhibitory currents2 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission3 |
No change |
Whole-cell patch clamp |
P4-p9 |
| Neurophysiology |
Synaptic neuroreceptor ratio (nmdar/ampar) dependent transmission2 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Synaptic plasticity1 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Synaptic transmission: excitatory1 |
No change |
Whole-cell patch clamp |
Unreported |
| Neurophysiology |
Tonic currents through extrasynaptic receptors3 |
No change |
Whole-cell patch clamp |
P11-p15 |
| Neurophysiology |
Voltage sensitivity of n-methyl d-aspartate (nmda) receptors2 |
No change |
Whole-cell patch clamp |
Unreported |
| Physiological parameters |
Digestive system function: gastrointestinal motility: peristaltic reflexes5 |
No change |
Measurement of colonic motility |
8-12 weeks |
| Sensory |
Vision1 |
No change |
Morris water maze test |
2-4 months |
| Social behavior |
Inanimate object preference2 |
No change |
Novel object recognition test |
Unreported |
| Social behavior |
Social approach2 |
No change |
Three-chamber social approach test |
Unreported |
|
| Not Reported: |
Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior, |
