Summary Information
Duplications at the 15q11-q13 loci on the maternally-derived chromosome are among the most prevalent CNVs in autistic populations. The corresponding duplication on the paternal chromosome is thought to confer less risk towards ASD pathogenesis. Deletions in this region are responsible for Angelman syndrome (deletion on maternal chromosome 15) and Prader-Willi syndrome (deletion on paternal chromosome 15)
Additional Locus Information
References
Major Reports
Minor Reports
No Minor Reports
Cases
Controls
Cases
Controls
Cases
Controls
Cases
Controls
h15q11-q13->m7qB5-qC
# of References: 7
Mouse Chromosome Information
This mouse model features a duplication in the qB5-qC loci of chromosome 7, proximal to Herc2 and distal to Mrkn3. It is syntenic to common breakpoints of duplications in human chromosome 15q11-q13.
Model Summary
This is a mouse model of 15q11-q13 loci duplication commonly observed in autistic populations. Mice with this duplication display autism-associated traits such as decreased sociability, altered vocalizations, and increased anxiety when the duplication is located on the paternal, but not the maternal, chromosome.
References
M_DP(7)_1_HT_P
M_DP(7)_1_HT_P_GEPH-GFP
M_DP(7)_1_HT_P_PSD95-GFP
M_DP(7)_2_HT_M
M_DP(7)_2_HT_M_FLUOXETINE-1
M_DP(7)_2_HT_M_FLUOXETINE-2
M_DP(7)_2_HT_M_FLUOXETINE-3
M_DP(7)_1_HT_P
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Motor phenotype | General locomotor activity 5 |
Decreased
Description:
Decreased spontaenous locomotor activity
Exp Paradigm: Open Field Test |
Open field test | |
Motor phenotype | Gait 3 |
Increased
Description:
Dp(7) mice show increased stride length and stance width compared to wild type littermate controls. They also show concomitantly reduced stride frequency.
|
Footprint analysis | 4-20 weeks |
Neurophysiology | Anatomical projections and connectivity: purkinje cell-climbing fiber connections 3 |
Increased
Description:
A significantly higher number of Purkinje cells, examined from adult Dp(7) mice as well, receive inputs from more than one (2-3) climbing fiber, unlike littermate controls (most of them receive input from 1 climbing fiber).
|
Whole-cell patch clamp | 4-20 weeks |
Neurophysiology | Synaptic plasticity: cerebellar ltd 3 |
Decreased
Description:
Normal protocol for cerebellar LTD generation does not induce LTD in Dp(7) mice, unlike in littermate controls. It should be noted that if LTP is induced prior to LTD, to relieve saturation of maximally depressed synapses, normal LTD can be induced in the cerebellar Purkinje cells of Dp(7) mice
|
Whole-cell patch clamp | 4-20 weeks |
Neurophysiology | Neurotransmitter release: catecholamines 2 |
Increased
Description:
Increased epinephrine levels in cerebellum and cortex
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Neurotransmitter release: serotonin 5 |
Decreased
Description:
Decreased levels of 5-HT and 5-HIAA in several brain regions
Exp Paradigm: HPLC analysis of brain lysates |
High-performance liquid chromatography (hplc) | |
Neurophysiology | Neurotransmitter release: catecholamines 2 |
Increased
Description:
Increased dopamine levels in frontal cortex
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Neurotransmitter release: serotonin 5 |
Decreased
Description:
Decreased levels of 5-HT across all brain regions
Exp Paradigm: HPLC analysis of brain lysates |
High-performance liquid chromatography (hplc) | P7-P21 |
Neurophysiology | Anatomical projections and connectivity: purkinje cell-climbing fiber connections 3 |
Increased
Description:
A significantly higher number of Purkinje cells, examined from young Dp(7) mice, receive inputs from more than one (2-3) climbing fiber, unlike littermate controls.
|
Whole-cell patch clamp | P10-P12 |
Neurophysiology | Neurotransmitter release: serotonin 2 |
Decreased
Description:
Decreased 5HT levels in frontal cortex, hippocampus, midbrain, and striatum
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Social behavior | Social interaction 1 |
Decreased
Description:
Decreased sociability demonstrated by decreased interaction with novel mouse
Exp Paradigm: Three-chamber social interaction test |
Three-chamber social approach test | |
Physiological parameters | Core body temperature 5 |
Decreased
Description:
Decreased body temperature
|
9-13 weeks | |
Communications | Ultrasonic vocalization: isolation induced 1 |
Increased
Description:
Increased number of ultrasonic vocalizations
Exp Paradigm: USV measurements |
Monitoring ultrasonic vocalizations | P5-P14 |
Communications | Ultrasonic vocalization: isolation induced 1 |
Abnormal
Description:
Abnormal frequency distribution of ultrasonic vocalizations
Exp Paradigm: Frequency analysis of USV |
Monitoring ultrasonic vocalizations | P7, P14 |
Communications | Audible vocalization 1 |
Decreased
Description:
Decreased number of audible and ultrasonic vocalizations in response to intruder
Exp Paradigm: Resident-intruder paradigm followed by vocalization measurements |
Resident-intruder test | |
Developmental profile | Size/growth 1 |
Increased
Description:
Increased body weight
Exp Paradigm: General Observations |
General observations | 15-20 weeks |
Developmental profile | Size/growth 5 |
Increased
Description:
Increased body weight
Exp Paradigm: General Observations |
General observations | 9-13 weeks |
Emotion | Anxiety 5 |
Increased
Description:
Increased anxiety-like behavior
Exp Paradigm: Open Field Test; Novelty supressed feeding test-Novelty-suppressed feeding paradigm |
Novelty-induced hypophagia | 9-13 weeks |
Emotion | Exploratory activity 5 |
Decreased
Description:
Decreased exploratory activity
Exp Paradigm: Y-maze task; marble burying test-Y-maze test |
Y-maze test | 9-13 weeks |
Emotion | Anxiety 1 |
Increased
Description:
Increased anxiety demonstrated by decreased time spent in open arms
Exp Paradigm: Elevated plus maze test |
Elevated plus maze test | |
Emotion | Exploratory activity 5 |
Decreased
Description:
Decreased exploratory activity
Exp Paradigm: Y-maze task; marble burying test-Marble-burying test |
Marble-burying test | 9-13 weeks |
Emotion | Anxiety 5 |
Increased
Description:
Increased anxiety-like behavior
Exp Paradigm: Open Field Test; Novelty supressed feeding test-Open field test |
Open field test | 9-13 weeks |
Learning & memory | Cognitive flexibility 1 |
Decreased
Description:
Decreased behavior flexibility
Exp Paradigm: Morris water maze test; Barnes maze test-Barnes maze test |
Barnes maze test | |
Learning & memory | Eye blink conditioning 3 |
Decreased
Description:
Dp(7) mice have decreased number of conditioned responses to eyeblink conditioning compared to littermate controls in the first phase of training and trials, showing reduced cerebellar dependent motor learning, attributed to reduced cerebellar plasticity and de novo acquisition. There was no impairment in the presentation of the response (eye closure), or in duration (peak time, amplitude etc) of CR , when generated.
|
Eyeblink conditioning | 4-20 weeks |
Learning & memory | Cued or contextual fear conditioning 1 |
Increased
Description:
Increased cued conditioning anomalies demonstrated by increased freezing score in altered contextual environment
Exp Paradigm: Cued and contextual conditioning task using 60 dB white noise tone and mild foot shock |
Fear conditioning test | |
Learning & memory | Cognitive flexibility 1 |
Decreased
Description:
Decreased behavior flexibility
Exp Paradigm: Morris water maze test; Barnes maze test-Morris water maze test |
Morris water maze test | |
Learning & memory | Eye blink conditioning 4 |
Decreased
Description:
There is a significant decrease in learning the conditioned response in patdp/+ or Dp(7) pat mice, compared to littermate controls
Exp Paradigm: Males only |
Eyeblink conditioning | 2-4 months |
Molecular profile | Metabolite levels: neurometabolites 2 |
Increased
Description:
Increased DOPAC levels in cerebellum, midbrain and frontal cortex
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Molecular profile | Protein expression level evidence 3 |
Increased
Description:
Dp(7) mice have increased expression of Ube3a in the cerebellum
|
Western blot | 4-20 weeks |
Molecular profile | Gene expression 1 |
Increased
Description:
Increased expression of MBII52 in brain
Exp Paradigm: RNA blot hybridization in brain |
Northern blot | |
Molecular profile | Metabolite levels: neurometabolites 5 |
Increased
Description:
Increased levels of DA and metabolies: HVA, DOPAC
Exp Paradigm: HPLC analysis of brain lysates |
High-performance liquid chromatography (hplc) | P7-P21 |
Molecular profile | Gene expression 1 |
Increased
Description:
Increased expression levels of Ndn, Snrpn, GABAa, Herc2
Exp Paradigm: Quantitative RT-PCR in brains |
Quantitative pcr (qrt-pcr) | |
Molecular profile | Metabolite levels: neurometabolites 2 |
Increased
Description:
Increased HIAA, a major metabolite of 5HT levels in frontal cortex and striatum
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Molecular profile | Rna modification 1 |
Increased
Description:
Increased RNA editing ratio in sites A, B, and D of 5-HT2cR RNA
|
||
Circadian sleep/wake cycle | Locomotor activity in diurnal cycle 5 | No change | Home cage behavior | 9-13 weeks |
Developmental profile | Mortality/lethality 1 | No change | General observations | |
Learning & memory | Cued or contextual fear conditioning 5 | No change | Fear conditioning test | 9-13 weeks |
Learning & memory | Eye blink conditioning 4 | No change | Eyeblink conditioning | 2-4 months |
Learning & memory | Eye blink conditioning: extinction and reactivation 3 | No change | Eyeblink conditioning | 4-20 weeks |
Learning & memory | Eye blink conditioning: extinction and reactivation 4 | No change | Eyeblink conditioning | 2-4 months |
Learning & memory | Spatial learning 1 | No change | Barnes maze test | |
Learning & memory | Spatial learning 1 | No change | Morris water maze test | |
Learning & memory | Spatial working memory 5 | No change | Y-maze test | |
Molecular profile | Dna methylation 1 | No change | ||
Molecular profile | Gene expression 1 | No change | Quantitative pcr (qrt-pcr) | |
Molecular profile | Protein expression level evidence 2 | No change | Western blot | 12-15 weeks |
Motor phenotype | Grip strength 5 | No change | Grip strength test | 9-13 weeks |
Motor phenotype | Motor coordination and balance 5 | No change | Accelerating rotarod test | 9-13 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Brain morphology 1 | No change | Histology | P0, P7,P14 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Cerebellar foliation 3 | No change | Immunohistochemistry | 4-20 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Cerebellar morphology 3 | No change | Immunohistochemistry | 4-20 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Cerebellar morphology: granule cell layer thickness 4 | No change | Histology | 2-4 months |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Cerebellar morphology: molecular layer thickness 4 | No change | Histology | 2-4 months |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: dendritic tree complexity 3 | No change | Sholl analysis | 4-20 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: dendritic tree complexity 4 | No change | Sholl analysis | 2-4 months |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine density 4 | No change | Sholl analysis | 2-4 months |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuronal number: purkinje cells 3 | No change | Immunohistochemistry | 4-20 weeks |
Neurophysiology | Neurotransmitter release 5 | No change | High-performance liquid chromatography (hplc) | P7-P21 |
Neurophysiology | Neurotransmitter release 5 | No change | High-performance liquid chromatography (hplc) | |
Neurophysiology | Synaptic plasticity: cerebellar ltp 3 | No change | Whole-cell patch clamp | 4-20 weeks |
Neurophysiology | Synaptic transmission 3 | No change | Whole-cell patch clamp | 4-20 weeks |
Physiological parameters | Bioactive compound levels: tetrahydrobiopterin 2 | No change | High-performance liquid chromatography with electrochemical detection (hplc-ec) | 12-15 weeks |
Sensory | Pain or nociception 5 | No change | Hot plate test | 9-13 weeks |
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, | |||
References: | 1: Nakatani J , et al. 2009 , 2: Farook MF , et al. 2012 , 3: Piochon C , et al. 2014 , 4: Kloth AD , et al. 2015 , 5: Tamada K , et al. 2010 |
M_DP(7)_1_HT_P_GEPH-GFP
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Structural dendritic plasticity 1 |
Decreased
Description:
Dp(7) mice show reduced remodeling of gephyrin negative puncta in the SSC after sensory stimulation (chessboard whisker trimming) compared to wild type mice. Wild type mice show increased gain of gephyrin negatice puncta which receive intracortical input. Gephyrin positive puncta remain unaffected in both wild type and Dp(7) mice
Exp Paradigm: Turnover of Gephyrin-GFP negative puncta-associated spines was measured |
Two-photon microscopy | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 |
Increased
Description:
Dp(7) mice show increased turnover of Gephyrin-negative puncta associated spines in the SSC compared to wild type mice
Exp Paradigm: Turnover of Gephyrin-GFP negative puncta-associated spines was measured |
Two-photon microscopy | P21-P23 |
Neurophysiology | Neuronal activation following behavioral stimulation: c-fos levels 1 |
Decreased
Description:
Dp(7) mice have reduced density of C-Fos positive cells in the barrel cortex region corresponding to row C of whiskers, in layers 2/3 compared to wild type mice
Exp Paradigm: All whiskers except row C were removed and mice exposed to enriched environment for 1 h before sacrifice |
Immunohistochemistry | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine density 1 | No change | Two-photon microscopy | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 | No change | P21-P23 | |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density: excitatory 1 | No change | Two-photon microscopy | P21-P23 |
Neurophysiology | Neuronal activation following behavioral stimulation: c-fos levels 1 | No change | Immunohistochemistry | P21-P23 |
Not Reported: | Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior, | |||
References: | 1: Isshiki M , et al. 2014 |
M_DP(7)_1_HT_P_PSD95-GFP
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 |
Increased
Description:
Dp(7) mice show increased turnover of PSD95-positive puncta associated spines in the SSC compared to wild type mice
Exp Paradigm: Turnover of PSD95 -GFP positive puncta, present on spines, was measured |
Two-photon microscopy | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 |
Increased
Description:
Dp(7) mice show increased turnover of PSD95-positive puncta associated spines in the AFC compared to wild type mice
Exp Paradigm: Turnover of PSD-95 -GFP positive puncta of spines was measured |
Two-photon microscopy | P21-23, P14-P15 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 |
Increased
Description:
Dp(7) mice show increased turnover of PSD95-negative puncta associated spines in the AFC compared to wild type mice (this is slightly different from the turnover of PSD95 negative spines in the SSC)
Exp Paradigm: Turnover of PSD-95 -GFP negative puncta of spines was measured |
Two-photon microscopy | P14-P15 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine density 1 | No change | Two-photon microscopy | P21-P23, P14-P15 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine density 1 | No change | Two-photon microscopy | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: spine turnover 1 | No change | Two-photon microscopy | P21-P23 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density: excitatory 1 | No change | Two-photon microscopy | P21-P23, P14-P15 |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density: excitatory 1 | No change | Two-photon microscopy | P21-P23 |
Not Reported: | Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Molecular profile, Motor phenotype, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior, | |||
References: | 1: Isshiki M , et al. 2014 |
M_DP(7)_2_HT_M
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density: inhibitory 3 |
Decreased
Description:
Mutants show reduction in the number of vesicular GABA transporter (VGAT) positive synapses in layers 2 and 3 but not in layers 4 and 6 of the somatosensory cortex compared to controls. Mutants show a reduction in symmetric synapses (which indicate inhibitory synapses) compared to controls.
|
Immunohistochemistry | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuroreceptor levels: serotonin 3 |
Decreased
Description:
Mutants show decrease in midbrain serotonin levels compared to controls.
|
High-performance liquid chromatography (hplc) | 9-10 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuroreceptor levels: gaba-r: gabaa 3 |
Increased
Description:
Mutants show increased expression of GABA-A receptor subunits Gabra5, Gabrb3, and Gabrg3, compared to controls.
|
Quantitative pcr (qrt-pcr) | 3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synaptic morphology 3 |
Abnormal
Description:
Mutants show a decrease in symmetric but no change in asymmetric synapses compared to controls.
|
Electron microscopy | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: dendritic length 3 |
Decreased
Description:
Mutants show decrease in maximum apical dendritic length compared to controls, in layer 2-3 pyramidal neurons of the somatosensory cortex.
|
Immunohistochemistry | 2-3 weeks |
Neurophysiology | Ion influx and permeability: calcium 3 |
Abnormal
Description:
Mutants show no change in the size of the peak response area of the principal barrel to a single whisker stimulation compared to controls. Mutants show an increase in the responsive surrounding area compared to controls.
Exp Paradigm: Transgenic mouse expressing the GFP-Calmodulin fusion protein, GCaMP7 were used for calcium imaging. |
Calcium imaging | 2-3 weeks |
Neurophysiology | Spontaneous post synaptic event amplitude: excitatory currents 3 |
Decreased
Description:
Mutants show decreased amplitude of sEPSCs in the DRN neurons of the lateral wing and the ventromedial nuclei, compared to controls.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Decay kinetics of evoked post synaptic currents 3 |
Decreased
Description:
Mutants show smaller peak amplitude and slower decay slope percentage in the principal area of the somatosensory cortex compared to controls, indicating decreased responsiveness to the principal whisker.
Exp Paradigm: Transgenic mouse expressing the GFP-Calmodulin fusion protein, GCaMP7 were used for calcium imaging. |
Calcium imaging | 2-3 weeks |
Neurophysiology | Neuronal activation 3 |
Decreased
Description:
Mutants show reduced regional activity in the DRN, hippocampus and anterior cingulate cortex, compared to controls.
Exp Paradigm: DRN activity was measured by PET imaging of regional cerebral glucose levels using a 2-[^18F] fluoro- 2-deoxy-D-glucose ([^18F]FDG) probe. |
Positron emission tomography (pet) imaging | 5-8 weeks |
Neurophysiology | Intrinsic membrane properties 3 |
Abnormal
Description:
Mutants show higher input resistance compared to controls but no change in cellular capacitance and resting membrane potential compared to controls.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Neurotransmitter release: catecholamines 2 |
Increased
Description:
Increased norepinephrine levels in striatum, hippocampus and cerebellum
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Action potential firing 3 |
Increased
Description:
Mutants show increased excitability of pyramidal neurons in layers 2-3 of the somatosensory cortex, compared to controls, measured by an increase of area under the curve computed from action potential frequency plots.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Miniature post synaptic current frequency: inhibitory 3 |
Decreased
Description:
Mutants show decrease in the frequency of mIPSCs compared to controls in pyramidal neurons of layer 2-3 of the somatosensory cortex.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Hyperpolarization activated cation currents 3 |
Decreased
Description:
Mutants show smaller hyperpolarization activated cation currents compared to controls.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Neurotransmitter release: catecholamines 2 |
Increased
Description:
increased epinephrine levels in striatum and frontal cortex, not midbrain
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Membrane potential 3 |
Increased
Description:
Mutant 5HT neurons in the DRN were hyperpolarized compared to controls.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Synaptic transmission: excitatory 3 |
Decreased
Description:
Mutants show reduced excitatory synaptic transmission onto 5-HT neurons compared to controls.
|
Whole-cell patch clamp | 2-3 weeks |
Neurophysiology | Decay kinetics of miniature post synaptic currents 3 |
Decreased
Description:
Mutants show slower decay time of mIPSCs compared to controls in pyramidal neurons of layer 2-3 of the somatosensory cortex, compared to controls.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Neurotransmitter release: catecholamines 2 |
Increased
Description:
Increased dopamine levels in cerebellum
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Sensory | Sensory-evoked response: excitation: tactile stimulus 3 |
Abnormal
Description:
Mutants show no change in firing properties in spiking neurons compared to controls. Mutants show increase in amplitudes of surrounding whisker responses compared to controls. Mutants show no change in the amplitudes of principal whisker responses compared to controls. Mutants show lower tuning of whisker selectivity compared to controls.
Exp Paradigm: In vivo patch-clamp recordings of layer 2/3 of the cerebral cortex was performed to measure the responsiveness of a single neuron to whisker stimuli. |
Whole-cell patch clamp | 2-3 weeks |
Social behavior | Social approach 3 |
Decreased
Description:
Mutants spent less time with a caged novel mouse than around an empty cage, compared to controls.
|
Three-chamber social approach test | 9-12 weeks |
Communications | Ultrasonic vocalization: isolation induced 3 |
Increased
Description:
Mutants show increase in the number of USV calls compared to controls.
|
Monitoring ultrasonic vocalizations | P7 |
Emotion | Exploratory activity 3 |
Decreased
Description:
Mutants show reduced exploratory activity compared to controls.
|
Open field test | 9-12 weeks |
Emotion | Anxiety 3 |
Increased
Description:
Mutants spent less time in the center of the open field compared to controls.
|
Open field test | 9-12 weeks |
Molecular profile | Gene expression 1 |
Increased
Description:
Increased mRNA expression levels of Ndn, Ube3a, GABAa, Herc2
Exp Paradigm: Quantitative RT-PCR in brains |
Quantitative pcr (qrt-pcr) | |
Molecular profile | Protein expression level evidence 2 |
Increased
Description:
increased Ube3a protein expression in cerebellum and hippocampus
Exp Paradigm: Western Blot Analysis |
Western blot | 12-15 weeks |
Molecular profile | Metabolite levels: neurometabolites 2 |
Increased
Description:
Increased DOPAC levels in striatum
Exp Paradigm: High-Performance Liquid Chromatography with Electrochemical Detection |
High-performance liquid chromatography (hplc) | 12-15 weeks |
Molecular profile | Metabolite level quantification 3 |
Decreased
Description:
Mutants show decrease in midbrain serotonin metabolite 5-HIAA levels compared to controls.
|
High-performance liquid chromatography (hplc) | 9-10 weeks |
Communications | Ultrasonic vocalization: isolation induced 1 | No change | Monitoring ultrasonic vocalizations | P5 - P14 |
Developmental profile | Mortality/lethality 1 | No change | General observations | |
Emotion | Anxiety 1 | No change | Elevated plus maze test | |
Learning & memory | Cognitive flexibility 3 | No change | 9-12 weeks | |
Learning & memory | Cognitive flexibility 1 | No change | Barnes maze test | |
Learning & memory | Cued or contextual fear conditioning 1 | No change | Fear conditioning test | |
Learning & memory | Spatial reference memory 3 | No change | Morris water maze test | 9-12 weeks |
Learning & memory | Spatial working memory 3 | No change | Morris water maze test | 9-12 weeks |
Molecular profile | Dna methylation 1 | No change | ||
Molecular profile | Gene expression 3 | No change | Quantitative pcr (qrt-pcr) | 2 weeks |
Molecular profile | Gene expression 1 | No change | Quantitative pcr (qrt-pcr) | |
Molecular profile | Gene expression 1 | No change | Northern blot | |
Molecular profile | Rna modification 1 | No change | ||
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: dendritic tree complexity 3 | No change | Immunohistochemistry | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Dendritic architecture: dendritic tree complexity 3 | No change | Immunohistochemistry | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuronal number: inhibitory neurons 3 | No change | Immunohistochemistry | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuroreceptor levels: gaba-r: gabaa 3 | No change | Quantitative pcr (qrt-pcr) | 3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density 3 | No change | Immunohistochemistry | 2-3 weeks |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Synapse density: excitatory 3 | No change | Immunohistochemistry | 2-3 weeks |
Neurophysiology | Action potential properties: amplitude, rate of depolarization and repolarization 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Decay kinetics of miniature post synaptic currents 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Miniature post synaptic current amplitude: excitatory 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Miniature post synaptic current amplitude: inhibitory 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Miniature post synaptic current frequency: excitatory 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Neuronal activation 3 | No change | Positron emission tomography (pet) imaging | 5-8 weeks |
Neurophysiology | Neurotransmitter release: catecholamines 2 | No change | High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Neurotransmitter release: serotonin 2 | No change | High-performance liquid chromatography (hplc) | 12-15 weeks |
Neurophysiology | Presynaptic function: paired-pulse facilitation 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Spontaneous post synaptic event amplitude: inhibitory currents 3 | No change | Whole-cell patch clamp | 4-8 weeks |
Neurophysiology | Spontaneous post synaptic event frequency: excitatory currents 3 | No change | Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Spontaneous post synaptic event frequency: inhibitory currents 3 | No change | Whole-cell patch clamp | 4-8 weeks |
Physiological parameters | Bioactive compound levels: tetrahydrobiopterin 2 | No change | High-performance liquid chromatography with electrochemical detection (hplc-ec) | 12-15 weeks |
Not Reported: | Circadian sleep/wake cycle, Communications, Developmental profile, Emotion, Immune response, Learning & memory, Maternal behavior, Motor phenotype, Neuroanatomy / ultrastructure / cytoarchitecture, Neurophysiology, Physiological parameters, Repetitive behavior, Seizure, Sensory, Social behavior, | |||
References: | 1: Nakatani J , et al. 2009 , 2: Farook MF , et al. 2012 , 3: Nakai N , et al. 2017 |
M_DP(7)_2_HT_M_FLUOXETINE-1
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Neuroanatomy / Ultrastructure / Cytoarchitecture | Neuroreceptor levels: serotonin 1 |
Ameliorated
Description:
FLX treatment increased the midbrain serotonin levels in mutants but not to control levels.
|
High-performance liquid chromatography (hplc) | 9-10 weeks |
Neurophysiology | Membrane potential 1 |
Refractory
Description:
FLX treatment did not restore the hyperpolarized membrane potential in mutants.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Spontaneous post synaptic event amplitude: excitatory currents 1 |
Restored
Description:
FLX treatment restored the decreased sEPSC amplitudes to control levels at the ventromedial DRN and the lateral wing DRN in mutants.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Decay kinetics of miniature post synaptic currents 1 |
Refractory
Description:
FLX treatment did not restore the longer decay time of mIPSCs in mutant pyramidal neurons of layer 2-3 of the somatosensory cortex.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Spontaneous post synaptic event frequency: inhibitory currents 1 |
Side effect
Description:
FLX treatment enhanced spontaneous IPSC frequency in the mutants.
Exp Paradigm: sIPSCs were recorded from layer2/3 pyramidal neurons in the somatosensory cortex. |
Whole-cell patch clamp | 4-8 weeks |
Neurophysiology | Miniature post synaptic current frequency: inhibitory 1 |
Ameliorated
Description:
FLX treatment increased the decrease in the frequency of mIPSCs in mutant pyramidal neurons of layer 2-3 of the somatosensory cortex.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Decay kinetics of miniature post synaptic currents 1 |
No adverse effect
Description:
FLX treatment did not change the 10-90% rise times of mIPSCs in pyramidal neurons of layer 2-3 of the somatosensory cortex in mutants.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Spontaneous post synaptic event frequency: excitatory currents 1 |
No adverse effect
Description:
FLX treatment had no adverse effect on the frequency of sEPSCs at the ventromedial DRN and the lateral wing DRN in mutants.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Miniature post synaptic current amplitude: inhibitory 1 |
No adverse effect
Description:
FLX treatment did not change the amplitude of mIPSCs in pyramidal neurons of layer 2-3 of the somatosensory cortex in mutants.
|
Whole-cell patch clamp | 5-8 weeks |
Neurophysiology | Action potential firing 1 |
Restored
Description:
FLX treatment suppressed the increased intrinsic excitability of pyramidal neurons in the somatosensory cortex.
|
Whole-cell patch clamp | 4-8 weeks |
Neurophysiology | Spontaneous post synaptic event amplitude: inhibitory currents 1 |
No adverse effect
Description:
FLX treatment did not change the amplitude of sIPSCs in mutants.
|
Whole-cell patch clamp | 4-8 weeks |
Social behavior | Social approach 1 |
Ameliorated
Description:
FLX treatment of mutants increased the amount of time the mice spent around a novel caged conspecific compared to untreated mutants.
|
Three-chamber social approach test | 9-12 weeks |
Emotion | Exploratory activity 1 |
Refractory
Description:
FLX treatment did not increase the reduced exploratory activity in mutants.
|
Open field test | 9-12 weeks |
Emotion | Anxiety 1 |
Refractory
Description:
FLX treatment does not increase the time spent in the center in mutants compared to controls.
|
Open field test | 9-12 weeks |
Learning & memory | Spatial reference memory 1 |
No adverse effect
Description:
FLX treatment shows no change in time spent in the target quadrant during the probe trial phase in mutants.
|
Morris water maze test | 9-12 weeks |
Learning & memory | Cognitive flexibility 1 |
No adverse effect
Description:
FLX treatment shows no change in time spent in the target quadrant during the reverse learning phase in mutants.
|
Morris water maze test | 9-12 weeks |
Learning & memory | Spatial working memory 1 |
No adverse effect
Description:
FLX treatment shows no change in time spent in the target quadrant during the acquisition phase in mutants.
|
Morris water maze test | 9-12 weeks |
Molecular profile | Metabolite level quantification 1 |
Ameliorated
Description:
FLX treatment elevated the decreased 5-HT metabolite 5-HIAA levels in midbrain in mutants but not to control levels.
|
High-performance liquid chromatography (hplc) | 9-10 weeks |
Not Reported: | Circadian sleep/wake cycle, Communications, Developmental profile, Immune response, Maternal behavior, Motor phenotype, Physiological parameters, Repetitive behavior, Seizure, Sensory, | |||
References: | 1: Nakai N , et al. 2017 |
M_DP(7)_2_HT_M_FLUOXETINE-2
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Communications | Ultrasonic vocalization: isolation induced 1 |
Ameliorated
Description:
FLX treatment reduced the number of USV calls by mutant pups but not to control levels.
|
Monitoring ultrasonic vocalizations | P7 |
Not Reported: | Circadian sleep/wake cycle, 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, | |||
References: | 1: Nakai N , et al. 2017 |
M_DP(7)_2_HT_M_FLUOXETINE-3
Category | Entity | Quantity | Experimental Paradigm | Age at Testing |
Communications | Ultrasonic vocalization: isolation induced 1 |
Restored
Description:
FLX treatment reduced the number of USV calls by mutant pups to controls levels.
|
Monitoring ultrasonic vocalizations | P7 |
Not Reported: | Circadian sleep/wake cycle, 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, | |||
References: | 1: Nakai N , et al. 2017 |