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M_NLGN3_21_KI_R451C
Model Details
Change
No Change
     
Phenotypic Profile
Category Entity Quantity Experimental Paradigm Age at Testing
Motor phenotype General locomotor activity: ambulatory activity2
Increased
Description: Mutants show increase in total distance travelled compared to controls.
Exp Paradigm: NA

Open field test 2-3 months
Motor phenotype General locomotor activity: ambulatory activity1
Increased
Description: Mutants mice travel a greater total distance compared to controls.
Exp Paradigm: NA

Partition test 2.3 to 6.6 months
Motor phenotype Hyperactivity2
Increased
Description: Mutants were hyperactive compared to controls.
Exp Paradigm: NA

Home cage behavior 2-3 months
Motor phenotype General locomotor activity: ambulatory activity1
Increased
Description: Mutants travel greater distances measured by total beam breaks during a 2-hr session in locomotor boxes compared to control.
Exp Paradigm: NA

Novel cage test 2.3 to 6.6 months
Neuroanatomy / Ultrastructure / Cytoarchitecture Anatomical projections and connectivity2
Abnormal
Description: Mutants show a larger proportion of neurons in the mpfc phase-locking in the quiet state compared to controls. mutants show a lower proportion of neurons in the mpfc phase-locking during social interaction compared to controls.
Exp Paradigm: NA

In vivo local field potential (lfp) recordings 2-3 months
Neurophysiology Action potential property: firing rate2
Abnormal
Description: Mutant neurons show higher firing rates during sniffing while another proportion show inhibition, compared to controls, indicating a tendency for decentralization and disruption in functional encoding through dysregulated discharges during social interaction.
Exp Paradigm: Firing rate changes in the quiet and social states were assessed by calculating the discrimination index.

In vivo local field potential (lfp) recordings 2-3 months
Neurophysiology Network excitability2
Abnormal
Description: Mutants showed reduced coupling between the low- gamma amplitude and the theta phase but displayed stronger and wider coupling between high gamma and theta rhythms, especially during social sniffing whereas local field potentials (lfps) from the wt mice showed modulation of both low-gamma and high-gamma amplitudes by the theta phase during social interaction with novel or familiar conspecific mice. mutants show weaker strength of modulation between low gamma and theta when exploring a new environment compared to controls. mutants show, decentralized gamma bursts within a single theta cycle during sniffing, indicating impairment of local coordinated network activity in the mpfc during social behaviors.
Exp Paradigm: NA

In vivo local field potential (lfp) recordings 2-3 months
Neurophysiology Intrinsic bursting events or spikes2
Decreased
Description: Mutants show impaired intrinsic excitability of mpfc fast spiking interneurons in response to step-current injection compared to controls, suggesting that the reduced excitability of fs interneurons in the mpfc of the mutant mice is associated with the social novelty deficit.
Exp Paradigm: NA

Whole-cell patch clamp 2-3 months
Neurophysiology Electroencephalogram (eeg) signature2
Decreased
Description: During social sniffing mutants showed lower gamma band activity (3090 hz) than the wt mice.
Exp Paradigm: NA

Electroencephalogram (eeg) 2-3 months
Neurophysiology Neuronal activation2
Decreased
Description: Mutants show decreased neuronal activation in the three-chamber test after social novelty compared to controls, measured by the number of c-fos expressing neurons. mutants show no change in neuronal activation in the three-chamber test after the sociability phase compared to controls, measured by the number of c-fos expressing neurons.
Exp Paradigm: Expression of the immediate-early gene c-fos was assessed in different brain regions of mice after each stage of the three-chamber test.

Immunohistochemistry 2-3 months
Sensory Startle response: acoustic stimulus1
Decreased
Description: Mutant mice show less acoustic startle to high decibel tones, compared to controls.
Exp Paradigm: Response to tones of increasing volume was measured.

Acoustic startle reflex test 2.3 to 6.6 months
Social behavior Social memory2
Decreased
Description: Mutants show decreased preference for the unfamiliar mouse compared to controls.
Exp Paradigm: NA

Three-chamber social approach test 2-3 months
Social behavior Nest building behavior1
Increased
Description: Mutants built slightly wider nests of similar heights compared to controls.
Exp Paradigm: NA

Nest building assay 2.3 to 6.6 months
Learning & memory Spatial reference memory1
Decreased
Description: Mutants show decreased preference for the target quadrant compared to controls, during the probe trial when the platform is removed on the 12th day after 11 days training. mutants show decreased preference for the target quadrant, 5 days after reversal training, compared to controls.
Exp Paradigm: NA

Morris water maze test 2.3 to 6.6 months
Molecular profile Protein binding3
Decreased
Description: reduced the NLGN3 pulldown efficiency by NRXN1β and PTPδA3Bâ?? to 40% and 20% of wild-type, respectively

Co-immunoprecipitation Adult
Molecular profile Signaling3
Abnormal
Description: lack of Shank2 and gephyrin on the PTPδA3Bâ?? beads in mutant cortical neurons; NRXN1β-induced accumulation of Shank2 and gephyrin was unaltered and significantly increased in Nlgn3R/C cortical neurons, respectively, suggesting that the Nlgn3 R/C mutation impairs the non-canonical pathway

Immunostaining Adult
Emotion Anxiety1 No change Open field test 2.3 to 6.6 months
Emotion Anxiety1 No change Elevated plus maze test 2.3 to 6.6 months
Emotion Anxiety2 No change Open field test 2-3 months
Emotion Anxiety1 No change Light-dark exploration test 2.3 to 6.6 months
Emotion Exploratory activity: habituation1 No change Olfactory discrimination test 2.3 to 6.6 months
Emotion Thigmotaxis1 No change Open field test 2.3 to 6.6 months
Emotion Thigmotaxis1 No change Morris water maze test 2.3 to 6.6 months
Learning & memory Cognitive flexibility1 No change Morris water maze test 2.3 to 6.6 months
Learning & memory Cued or contextual fear conditioning: memory of context1 No change Fear conditioning test 2.3 to 6.6 months
Learning & memory Cued or contextual fear conditioning: memory of cue1 No change Fear conditioning test 2.3 to 6.6 months
Learning & memory Object recognition memory2 No change Novel object recognition test 2-3 months
Learning & memory Spatial working memory2 No change Morris water maze test 2-3 months
Learning & memory Spatial working memory1 No change Morris water maze test 2.3 to 6.6 months
Learning & memory Spatial working memory2 No change Y-maze test 2-3 months
Motor phenotype General locomotor activity: ambulatory activity1 No change Open field test 2.3 to 6.6 months
Motor phenotype Motor learning1 No change Accelerating rotarod test 2.3 to 6.6 months
Motor phenotype Swimming ability1 No change Morris water maze test 2.3 to 6.6 months
Neurophysiology Intrinsic bursting events or spikes2 No change Whole-cell patch clamp 2-3 months
Sensory Olfaction1 No change Olfactory discrimination test 2.3 to 6.6 months
Sensory Olfaction1 No change Buried food test 2.3 to 6.6 months
Sensory Sensorimotor gating1 No change Prepulse inhibition 2.3 to 6.6 months
Social behavior Social approach2 No change Three-chamber social approach test 2-3 months
Social behavior Social interaction1 No change Partition test 2.3 to 6.6 months
Social behavior Social interaction: with juveniles1 No change Three-chamber social approach test 2.3 to 6.6 months
Not Reported: Circadian sleep/wake cycle,  Communications,  Developmental profile,  Immune response,  Maternal behavior,  Molecular profile,  Neuroanatomy / ultrastructure / cytoarchitecture,  Neurophysiology,  Physiological parameters,  Repetitive behavior,  Seizure,  Sensory,  
 
References: 1: Jaramillo TC , et al. 2017 , 2: Cao W , et al. 2018 , 3:  Yoshida T et al. 2021
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