Rare variants in the MEF2C gene have been identified with autism (Novara et al., 2010; Neale et al., 2012) as well as with mental retardation and developmental delay.
Molecular Function
The encoded protein is a transcription factor involved in diverse developmental processes including hematopoiesis, cardiogenesis and neurogenesis.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Refining the phenotype associated with MEF2C haploinsufficiency.
Genes influenced by MEF2C contribute to neurodevelopmental disease via gene expression changes that affect multiple types of cortical excitatory neurons
Mef2c is required for the early development of the heart, it is not necessary for the formation of the heart after looping morphogenesis. Conditional embryonic deletion of Mef2c in cortical and hippocampal excitatory neurons decreases cortical network activity by increasing inhibitory and decreasing excitatory synaptic transmission. Mef2c mutant mice exhibit deficits in social approach, learnig and memory, and ultrasonic vocalization. Mef2c mutant mice also display stereotypy and hyperactivity.
References
Type
Title
Author, Year
Primary
Generation of conditional Mef2cloxP/loxP mice for temporal- and tissue-specific analyses.
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Cre-loxP mediated deletion of exon 2 of Mef2c gene with Cre recombinase under control of EIIA- promoter which is expressed in all tissues, including germ cells.
Allele Type: Targeted (Conditional)
Strain of Origin: 129S6
Genetic Background: Not Specified
ES Cell Line: W4
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 2 of the Mef2c gene using aMyHC-cre (MCH-cre), in cardiac muscle cells
Allele Type: Conditional loss-of-function
Strain of Origin: 129S6
Genetic Background: Not Specified
ES Cell Line: W4
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 2 of the Mef2c gene using MLC2V-cre(Myl2-cre), in cardiac ventricular muscle starting E8
Allele Type: Conditional loss-of-function
Strain of Origin: 129S6
Genetic Background: Not Specified
ES Cell Line: W4
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Cre-loxP mediated deletion of exon 2 of Mef2c gene specific to radial glial cells during late embryogenesis with cre under the control of a human GFAP promoter.
Allele Type: Targeted (Conditional)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: 129SvEv
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Overexpression of superactive Mef2c-VP16 protein under the control of the rat neuron-specific enolase (NSE) promoter/enhancer.
Allele Type: Targeted (Overexpression)
Strain of Origin: Not Specified
Genetic Background: Not Specified
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exon 2 of the Mef2c gene using Emx1-cre, in the neurons and glia of the neocortex, hippocampus and pallium starting E10.5
Allele Type: Conditional loss-of-function
Strain of Origin: SVeV-129/C57BL/6J
Genetic Background: SVeV-129/C57BL/6J
ES Cell Line: 129SvEv
Mutant ES Cell Line: Not Specified
Model Source: Not Specified
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mef2c heterozygous knockout mice were generated by crossing mice with the second Mef2c exon deleted (PMID 9162005) with their WT littermates.
Allele Type: Knockout
Strain of Origin: C57BL/6J
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: PMID 9162005
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Mef2c conditional heterozygous (mef2c-chet) mice were generated by crossing mef2c-flox mice with cell typeâ??selective cre-expressing transgenic mice [pcp2-cre]
Allele Type: Conditional knockout
Strain of Origin: 129S7/SvEvBrd-Hprt+
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Mef2c conditional heterozygous (mef2c-chet) mice were generated by crossing mef2c-flox mice with cell typeâ??selective cre-expressing transgenic mice [cx3cr1creer/creer]. recombination was induced at p1-p3 by tamoxifen treatment in cx3cr1creer;eyfp; ai14 mice and tdtomato expression was used as a repotter.
Allele Type: Conditional knockout
Strain of Origin: 129S7/SvEvBrd-Hprt+
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Mef2c conditional heterozygous (mef2c-chet) mice were generated by crossing mef2c-flox mice with cell typeâ??selective cre-expressing transgenic mice [emx1-cre]. construct is identical to model m_mef2c_6_cko_hm but on a different background.
Allele Type: Conditional knockout
Strain of Origin: 129S7/SvEvBrd-Hprt+
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory
Model Type:
Genetic LOF
Model Genotype:
Heterozygous
Mutation:
Mef2c conditional heterozygous (mef2c-chet) mice were generated by crossing mef2c-flox mice with cell typeâ??selective cre-expressing transgenic mice [pv-cre]
Allele Type: Conditional knockout
Strain of Origin: 129S7/SvEvBrd-Hprt+
Genetic Background: C57BL/6J
ES Cell Line: Not Specified
Mutant ES Cell Line: Not Specified
Model Source: The Jackson Laboratory
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Mef2c^L35P knock-in mice were generated using CRISPR-Cas9-mediated gene targeting. The targeted allele has a missense mutation c.104T>C in exon 4, that results in amino acid change in the MEF2C product p.Leu35Pro. The heterozygous model has one wildtype allele and one knock-in allele.
Allele Type: ASD mutation
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Not specified
Mutant ES Cell Line: Model Source: Zi-Long Qiu
Description: Abnormal cardiovascular development - thin myocardium, lack of trabeculation in the ventricle
Exp Paradigm: Histological analysis of sagittal section of embryo
Description: Increased density of dendritic spines in dentate gyrus neurons
Exp Paradigm: Analysis of image stacks from z-series of golgi-stained dentate gyrus
Description: Decreased paired pulse facilitation (ppf)
Exp Paradigm: Whole-cell voltage clamp recordings of dentate gyrus granule neurons in response to second of two paired stimuli
Description: Decreased context-dependent fear conditioning, no change in cue-dependent fear conditioning
Exp Paradigm: Contextual- and cue- dependent learning
Description: Decreased density of dendritic spines in dentate gyrus granule neurons
Exp Paradigm: Analysis of image stacks from z-series of golgi-stained dentate gyrus
Description: Decrease in amplitude of both ampa and nmda mediated epsc in dentate granule neurons
Exp Paradigm: Whole-cell voltage clamp recordings of dentate gyrus granule neurons
Miniature post synaptic current frequency: excitatory1
Decreased
Description: Decreased frequency of mepsc in dentate granule neurons
Exp Paradigm: Whole-cell voltage clamp recordings of dentate gyrus granule neurons
Description: Decreased frequency (90%), decreased duration (50%), and decreased amplitude (50%) of spontaneous up states in acute slices from the somatosensory cortex of mef2c cko mice
Exp Paradigm: Field potential recordings
Ultrasonic vocalization: interaction induced: opposite sex stimulus1
Decreased
Description: Decreased number of opposite-sex-induced ultrasonic vocalizations (usvs) in mef2c cko male mice, featured as a 3-fold increase in the latency to the first call, 5-fold increase in unstructured usvs, a decrease in complex, but no change in simple, usvs, and a decrease in the maximum usv frequency and the mean frequency at the end of calls
Exp Paradigm: Monitoring ultrasonic vocalizations
Cued or contextual fear conditioning: memory of context1
Decreased
Description: Mef2c cko mice have decreased learning and memory in contextual fear conditioning tests relative to wildtype controls
Exp Paradigm: Fear conditioning test: a training protocol is used to pair three white noise tones (cs) with a foot shock (us) presented 1 min after the end of the cs; the memory is tested 24 hr after training sessions
Cued or contextual fear conditioning: memory of cue1
Decreased
Description: Mef2c cko mice have decreased learning and memory in cued fear conditioning tests relative to wildtype controls
Exp Paradigm: Fear conditioning test: a training protocol is used to pair three white noise tones (cs) with a foot shock (us) presented 1 min after the end of the cs; the memory is tested 24 hr after training sessions
Description: Mutants show decrease in the number of proliferating cells (pcna), developing neurons (dcx) and brdu labelled neun cells compared to controls.
Exp Paradigm: 8-week-old mice were injected intraperitoneally twice daily for 5 consecutive days with brdu.
Description: Mutants show decrease in the expression of vgat in the hippocampus, a marker of inhibitory synapses, compared to controls.
Exp Paradigm: NA
Dendritic architecture: dendritic tree complexity1
Decreased
Description: Mutants show decreased complexity of the dendritic tree compared to controls. mutants show decreased dendritic interactions and decreased numbers of secondary, tertiary, quaternary and quinary dendritic branches compared to controls.
Exp Paradigm: Sholl analysis was performed.
Description: Mutants show decreased neuronal cell size compared to controls.
Exp Paradigm: Visualized via retroviral-mediated gene transduction of mcherry.
Description: Mutants show decreased paired-pulse facilitation compared to controls.
Exp Paradigm: Ppf was tested by applying two pulses with interstimulus intervals ranging from 20 to 200 ms.
Miniature post synaptic current amplitude: excitatory2
Decreased
Description: Decreased input-selective glutamatergic synaptic transmission indicated by reduction in the amplitude of evoked excitatory postsynaptic currents, suggesting a reduction in presynaptic and/or postsynaptic transmission when stimulated in layer 2/3 and layer 5 but not layer 4; decreased ampa mediated mepsc amplitude indicating decreased ampa-mediated postsynaptic strength
Description: Mutants show increased e/i frequency and e/i amplitude ratios compared to controls, indicating a functional e/i imbalance.
Exp Paradigm: Acsf was used as the external bath solution, with 50 m picrotoxin and 1 m tetrodotoxin (ttx) to isolate spontaneous mepscs.
Description: Increase in paired pulse facilitation ratio of local horizontal inputs indicating a decrease in presynaptic release probability when stimulated in layer 2/3 but not layer 4
Description: Mutants show increase in the number of neurons staining for active caspase-3 and for terminal deoxynucleotidyl transferase dutp nick end labeling (tunel) in the ca3 region of the hippocampus, compared to controls.
Exp Paradigm: Immunohistochemistry: caspase-3
Miniature post synaptic current amplitude: inhibitory1
Decreased
Description: Mutants show decreased mipsc amplitude compared to controls.
Exp Paradigm: Acsf was used as the external bath solution, with 10 m 6-cyano-7-nitroquinoxaline-2,3-dione (cnqx), 50 m (2r)-amino-5- phosphonopentanoate(ap5), and 1 m ttx to isolate spontaneous mipscs.
Miniature post synaptic current frequency: inhibitory1
Decreased
Description: Mutants show decreased mipsc frequency and increased inter-event interval compared to controls.
Exp Paradigm: Acsf was used as the external bath solution, with 10 m 6-cyano-7-nitroquinoxaline-2,3-dione (cnqx), 50 m (2r)-amino-5- phosphonopentanoate(ap5), and 1 m ttx to isolate spontaneous mipscs.
Description: Mutants show increase in the number of neurons staining for active caspase-3 and for terminal deoxynucleotidyl transferase dutp nick end labeling (tunel) in the ca3 region of the hippocampus, compared to controls.
Exp Paradigm: Detection of apoptosis using the tunel assay
Description: Mutants show decreased ltp in the hippocampal ca1 region compared to controls.
Exp Paradigm: Ltp was induced by applying high-frequency stimulation consisting of three 100 hz pulses (duration: 1 s, interval: 20 s).
Miniature post synaptic current amplitude: excitatory1
Decreased
Description: Mutants show a slight reduction in mepsc amplitudes compared to controls.
Exp Paradigm: Acsf was used as the external bath solution, with 50 m picrotoxin and 1 m tetrodotoxin (ttx) to isolate spontaneous mepscs.
Miniature post synaptic current frequency: excitatory1
Increased
Description: Mutants show an increase in mepsc frequency and decreased inter-event interval compared to controls.
Exp Paradigm: Acsf was used as the external bath solution, with 50 m picrotoxin and 1 m tetrodotoxin (ttx) to isolate spontaneous mepscs.
Description: Mutants spend less time interacting with an unfamiliar mouse compared to controls.
Exp Paradigm: Durations and number of visits to the chamber with the unfamiliar mouse were recorded.
Description: Mutants showed no preference for the target quadrant over the opposite quadrant compared to controls, during the probe test trials.
Exp Paradigm: NA
Description: Mutants show decreased expression of mef2c protein compared to controls. mutants show decreased expression of mef2c transcript compared to controls.
Exp Paradigm: Western blot
Description: Mutants show increase in protein levels of vglut2 compared to controls.
Exp Paradigm: Immunoblots were performed on synaptosome-enriched hippocampal lysates.
Description: Mutants show decreased transcript levels for vesicular -aminobutyric acid (gaba) transporter vgat (encoded by slc32a1) and ccl9 compared to controls.
Exp Paradigm: NA
Description: Mutants show decreased expression of mef2c protein compared to controls. mutants show decreased expression of mef2c transcript compared to controls.
Exp Paradigm: Quantitative pcr (qrt-pcr)
Description: Mutants show decrease in the levels of the synaptosomal proteins synaptophysin and gad65 compared to controls.
Exp Paradigm: Immunoblots were performed on synaptosome-enriched hippocampal lysates. gad65 is a marker of inhibitory synapses.
Description: Mutants mice show abnormal gene expression in biogroups of neurogenesis, neuronal differentiation, synaptic function (downregulated), and neuronal cell death (upregulated), compared to controls.
Exp Paradigm: NA
Description: Reduced mepsc frequency and amplitude and decreased evoked mepsc amplitude in layer 2/3 pyramidal neurons indicate a decrease in excitatory synaptic transmission
Description: Mef2c heterozygous knockin mice show a decrease in parvalbumin-positive neuronal density in retrosplenial cortex, visual cortex, somatosensory cortex and dentate gyrus, but no change in somatostatin-positive interneuron density in retrosplenial cortex, hippocampus, somatosensory cortex.
Exp Paradigm: parvalbumin, somatostatin
Description: Mef2c heterozygous knockin mice show decreased social interaction in the resident intruder test, measured by cumulative sniffing time. Test consisted in presenting an intruder mice in 4 consecutive trials, and a new intruder in a fifth trial.
Description: Mef2c heterozygous knockin mice show decreased social recognition in the resident intruder test. Test consisted in presenting an intruder mice in 4 consecutive trials, and a new intruder in a fifth trial. Mef2c heterozygous mice did not show an increase in sniffing behavior in the fifth trial with the novel intruder.
Description: Mef2c heterozygous knockin mice show increased time in open arms and decreased time in closed arms, indicating a decrease in anxiety-like behavior.
Description: Mef2c heterozygous knockin mice show a decrease in MEF2C expression in somatosensory cortex, dentate gyrus and lateral amygdala.
Exp Paradigm: Mef2c
