A number of mutations in the TBR1 gene have been identified in multiple individuals with ASD as described below. Two de novo loss-of-function variants and two de novo missense variants in TBR1 have been identified in simplex ASD cases (PMIDs 22495309, 23160955, 22495311); these variants were not observed in controls or in external databases. Functional analysis in Deriziotis et al., 2014 demonstrated that these four de novo TBR1 variants disrupt multiple aspects of TBR1 function, including interactions with co-regulators such as CASK and/or FOXP2, cellular localization, and transcriptional regulation (PMID 25232744). Analysis of rare coding variation in 3,871 ASD cases and 9,937 ancestry-matched or paternal controls from the Autism Sequencing Consortium (ASC) in De Rubeis et al., 2014 identified TBR1 as a gene meeting high statistical significance with a FDR 0.01, meaning that this gene had a 99% chance of being a true autism gene (PMID 25363760). This gene was identified in Iossifov et al. 2015 as a strong candidate to be an ASD risk gene based on a combination of de novo mutational evidence and the absence or very low frequency of mutations in controls (PMID 26401017). Microdeletions encompassing TBR1 have also been identified in patients with developmental delay/intellectual disability (PMIDs 23112752, 24458984). den Hoed et al., 2018 functionally characterized two previously identified de novo TBR1 missense variants seen in ASD probands (p.Trp271Cys from De Rubeis et al., 2014 and p.Lys389Glu from ORoak et al., 2014) and determined that both variants disrupted multiple aspects of TBR1 function, including cellular localization and interactions with CASK, FOXP1, and FOXP2; the authors of this study also determined that the rare inherited TBR1 missense variant p.Gln418Arg (originally reported in an ASD proband in Deriziotis et al., 2014) disrupted the interaction between TBR1 and BCL11A. Through international data sharing, Nambot et al., 2020 collected data from 25 previously unreported individuals with TBR1 variants and found that autistic features were frequently observed (19/25 individuals), with five individuals receiving a diagnosis of ASD according to DSM-IV and/or ADOS criteria. A two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in Zhou et al., 2022 identified TBR1 as a gene reaching exome-wide significance (P < 2.5E-06).
Molecular Function
Probable transcriptional regulator involved in developmental processes that is required for normal brain development.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations.
Deep brain stimulation of the Tbr1-deficient mouse model of autism spectrum disorder at the basolateral amygdala alters amygdalar connectivity, whole-brain synchronization, and social behaviors
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exons 2 and 3, which encode a putative DNA-binding domain, were replaced with a PGK-neo cassette via homologous recombination. Homozygous mutant animals were identified by Southern blot and PCR genotype analysis.
Allele Type: Targeted (knockout)
Strain of Origin: 129X1/SVJ
Genetic Background: 129X1/SVJX C57BL/6
ES Cell Line: JM-1
Mutant ES Cell Line: Model Source: MMRC
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exons 2 and 3, which encode a putative DNA-binding domain, were replaced with a PGK-neo cassette via homologous recombination. Heterozygous animals were crossed with golli-lacZ transgenic mice and breeded to produce homozygous Tbr1 Kos. Golli-LacZ is a subplate specific marker.
Allele Type: Targeted (knockout)
Strain of Origin: 129X1/SVJ
Genetic Background: 129X1/SVJX C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Exons 2 and 3, which encode a putative DNA-binding domain, were replaced with a PGK-neo cassette via homologous recombination.
Allele Type: Knockout
Strain of Origin: 129X1/SVJ
Genetic Background: 129X1/SVJX C57BL/6q
ES Cell Line: JM-1
Mutant ES Cell Line: null
Model Source: Yi-Ping Hsueh Lab (PMID 24441682)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Previously generated Tbr1 heterozygous mice, with PGK-neo cassette replacing exons 2 and 3 were backcrossed for 20 generations to C57BL/6 background.
Allele Type: Targeted (knockout)
Strain of Origin: 129X1/SVJ
Genetic Background: C57BL/6
ES Cell Line: JM-1
Mutant ES Cell Line: Model Source:
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
LoxP sites were inserted into introns 1 and 3, flanking Tbr1 exons 2 and 3. Beta-actin cre excision globally removed exons 2 and 3, including the T-box DNA binding region, similar to the constitutive null allele in M_Tbr1_1_KO_HM.
Allele Type: Knockout
Strain of Origin: Not reported
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: inGenious Targeting Laboratory (Ronkonkoma, NY)
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Conditional deletion of exons 2-3 of the Tbr1 gene using Ntsr-cre in neurons of cortical layer 6 and subplate starting ~E16.5
Allele Type: Conditional loss-of-function
Strain of Origin: Not reported
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: inGenious Targeting Laboratory (Ronkonkoma, NY)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Conditional heterozygous deletion of exons 2-3 of the Tbr1 gene using Ntsr-cre in neurons of cortical layer 6 and subplate starting ~E16.5
Allele Type: Conditional loss-of-function
Strain of Origin: Not reported
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: inGenious Targeting Laboratory (Ronkonkoma, NY)
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Heterozygous TBR1-K228E mice in a C57BL/6J background carrying a constitutive knock-in mutation of Tbr1 (K228E) in exon 1 of the Tbr1 gene. The mutation was previously identified in patients with ASD.
Allele Type: Transgenic
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: Cyagen
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Homozygous TBR1-K228E mice in a C57BL/6J background carrying a constitutive knock-in mutation of Tbr1 (K228E) in exon 1 of the Tbr1 gene. The mutation was previously identified in patients with ASD.
Allele Type: Transgenic
Strain of Origin: C57BL/6
Genetic Background: C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source: Cyagen
Model Type:
Genetic
Model Genotype:
Heterozygous
Mutation:
Tbr1^flox/flox mice with loxP sites inserted into introns 1 and 3, flanking Tbr1 exons 2 and 3, including the T-box DNA binding region, were crossed with Rbp4-Cre mice to delete Tbr1 in layer 5 projection neurons at P0, about 8 days after the expression of Tbr1 begins. tdTomatofl/+ (Ai14) mice were crossed with Tbr1f/f mice and used as an endogenous reporter.
Allele Type: Conditional knockout
Strain of Origin: NA
Genetic Background: C57BL/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: NA
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Tbr1^flox/flox mice with loxP sites inserted into introns 1 and 3, flanking Tbr1 exons 2 and 3, including the T-box DNA binding region, were crossed with Rbp4-Cre mice to delete Tbr1 in layer 5 projection neurons at P0, about 8 days after the expression of Tbr1 begins. tdTomatofl/+ (Ai14) mice were crossed with Tbr1f/f mice and used as an endogenous reporter.
Allele Type: Conditional knockout
Strain of Origin: NA
Genetic Background: C57BL/6
ES Cell Line: NA
Mutant ES Cell Line: NA
Model Source: NA
Model Type:
Genetic
Model Genotype:
Homozygous
Mutation:
Exons 2 and 3, which encode a putative DNA-binding domain, were replaced with a PGK-neo cassette via homologous recombination. Heterozygous animals were crossed with homozygous P2-IRES-tau-LacZ mice and breeded to produce homozygous Tbr1 Kos.
Allele Type: Targeted (knockout)
Strain of Origin: 129X1/SVJ
Genetic Background: 129X1/SVJX C57BL/6
ES Cell Line: Mutant ES Cell Line: Model Source:
Description: The cortical pioneer neurons were not arranged in the subplate and the cortical plate, even though they appeared to be normal in number and morphology in tbr1 null mice. whereas in control mice these neurons were labeled in the subplate and the cortical plate retrogradely.
Exp Paradigm: Dii crystals were placed in mid portion of the internal capsule
Description: In tbr1 null mice the cells that were to occupy superficial layers ( like in control mice) migrated to deeper layers or formed superficial clusters
Exp Paradigm: Brdu staining by injection on e16.5
Description: In tbr1 null mice the projections from the entorhinal cortex to the hippocampus (labeled retrogradely) were not arranged into layers 2 and 3, like in controls. however, the anterogradely labeled projections in the hippocampus appear to be intact ( the alveus and fimbria).
Exp Paradigm: Retrograde labelling required dii injection from the hippocampus and anterograde labeling required injections to the entorhinal cortex
Description: Tbr1 null mice have severe defects in the corticothalamic(ct), corpus callosum(cc) and thalamocortical (tc) pathways. the ct axons grew only till internal capsule, cc fibers terminated in probst bundle without crossing the midline, and retrograde tracing of tc neurons was abolished completely
Exp Paradigm: NA
Description: In tbr1 null mice glutamatergic and gabaergic neurons had an abnormal distribution. in the caudal cortex the glutamatergic neurons gormed large clusters, instead of being present in layer 5 ( like in controls). gabaergic cells were scattered among many layers instead of being concentrated in layer 5 as well.
Exp Paradigm: NA
Description: The periglomerular and granule cells - interneurons are present in tbr1 null mice, however their organization is distorted because of the lack of the mitral cell layer.
Exp Paradigm: Interneurons were labelled with the marker tyrosine hydroxylase using in sity hybridization
Description: Cortical efferent pathways were labeled using tag-1 and it was seen that ct axons did not reach the thalamus in tbr1 null mice, unlike controls. the results of dii tracing were confirmed in the cc, cp pathways as well (pnd 0.5).
Exp Paradigm: Tag-1 immunohistochemistry
Description: Tbr1 null mice do not have cerebellar peduncle (cp) neurons in the forebrain, but only in the lateral areas. in controls cp neurons are found all over the neocortex
Exp Paradigm: Dii injections in the ventrolateral midbrain were used to label cp neurons retrogradely
Description: In tbr1 null mice due to abnormal cell migration the cortical plate cells also do not migrate to the deep layers, and remain shifted in superficial positions.
Exp Paradigm: Brdu staining by injection on e13.5
Description: The lateral olfactory tract (lot), that connects primary olfactory cortex and the olfactory bulb, is absent in tbr1 null mice
Exp Paradigm: Dii staining and calretinin staining
Description: By e16.5 the cortical axons in tbr1 null mice terminated at the internal capsule, whereas in controls they reach the ventral thalamic. the tbr1 null mice had thalamic axons that remained at the internal capsule and curved laterally to the external capsule instead of growing straight through and therefore did not innervate the cortex
Exp Paradigm: NA
Description: The sensory relay axons of the thalamus were also misrouted to the external capsule (pnd 1.5)
Exp Paradigm: Serotonin immunohistochemistry
Description: In tbr1 null mice there is abnormal cell migration during embryonic development and the cells that should form the marginal zone and the subplate are found in superficial positions
Exp Paradigm: Brdu staining by injection on e10.5 and e11.5
Description: Retrograde dii labeling did not label dorsal thalamic neurons in tbr1 null mice, unlike controls, indicating that thalamic axons had not reached the cortex
Exp Paradigm: Dii was inejcted in the cortex
Description: There is a reduction in id-2, reelin and tbr-1 mrna in the olfactory bulb of tbr1 null mice
Exp Paradigm: Specific proteins or protein modifications measured
Description: Expression of reelin mrna was decreased in the preplate of tbr1 null mice, in the paleocortex, lateral and dorsal neocortex
Exp Paradigm: Specific proteins or protein modifications measured-in situ hybridization (ish): brain
Description: Expression of reelin mrna was decreased in the preplate of tbr1 null mice, in the paleocortex, lateral and dorsal neocortex
Exp Paradigm: Specific proteins or protein modifications measured- western blot
Description: Tbr1 null mice containing the golli-lacz had no or severely reduced expression of lacz in the preplate and subplate, unlike control animals. indicating lack of differentiation of the subplate
Exp Paradigm: Golli-lacz expression was measured using b- galactosidase histochemistry on brain sections
Description: Tbr1 null mice containing the golli-lacz had significantly reduced expression of lacz in the primary olfactory cortex.
Exp Paradigm: Golli-lacz expression was measured using b- galactosidase histochemistry on brain sections
Description: Tbr1 null mice containing the golli-lacz had significantly reduced expression of lacz in the olfactory cortex bulb.
Exp Paradigm: Golli-lacz expression was measured using b- galactosidase histochemistry on brain sections
Description: Synaptic NMDARs, as measured by colocalized GluN1 and synapsin1/2 puncta, were significantly decreased in the lateral and basal amygdala of Tbr1 heterozygote mice compared with wildtype mice.
Description: There is decreased connectivity and projections between the left and right (contralateral) amygdalae in tbr1 hets compared to wt littermates, indicated by reduced labeling of posterior part of anterior commissure
Exp Paradigm: Retrograde red beads were implanted into lateral amygdala. contralateral amygdalae were probed for fluorescent signals
Description: Defective connection between ipsilateral central amygdala and basolateral amygdala in tbr hets
Exp Paradigm: Fluorescent red beads of dii were implanted into the central amygdala
Description: Tbr1 het mice had lower number of cfos positive cells in the lateral amygdala, indicating fewer activated neurons in the region, compared to wt littemates
Exp Paradigm: C-fos positive cells were counted in the lateral and basal amygdala following the conditioned taste aversion test and the auditory fear conditioning test
Description: Tbr1 het mice had lower number of cfos positive cells in the basal amygdala, indicating fewer activated neurons in the region, compared to wt littemates
Exp Paradigm: C-fos positive cells were counted in the lateral and basal amygdala following the conditioned taste aversion test only
Description: Excitatory glutamatergic synaptic transmission mediated by AMPARs is significantly decreased in Tbr1 heterozygote mice. Half-maximal AMPAR EPSC amplitude is significantly reduced in Tbr1 heterozygote mice. Amplitude of evoked isolated NMDAR-mediated EPSCs, as well as the NMDAR/AMPAR EPSC ratio, is also significantly decreased in Tbr1 heterozygote mice on a control zinc diet.
Description: Wildtype mice on a normal zinc diet show a significant preference for a novel conspecific over a familiar conspecific, but Tbr1 heterozygote mice did not show a preference.
Description: Wildtype and Tbr1 heterozygote mice on a normal zinc diet both show a significant preference for a social stimulus conspecific compared to the empty cup in a chamber, but heterozygote mice show a significant decrease in this preference, compared to wildtype mice, measured by a preference index of time spent with social stimulus minus time spent with empty cup.
Description: Tbr1 het mice show no preference for cued food eaten by a demonstrator, compared to wt mice that prefer cued food
Exp Paradigm: Mice were observed to see if they preferred food eaten by a familiar demonstrator mouse ( cinnamon flavored food). as a control different flavoring of food was also used.
Description: Tbr1 het pups have much fewer ultrasonic vocalization emissions compared to wt littermates when separated from their mothers
Exp Paradigm: Frequency of vocalizations was analyzed
Description: Tbr1 heterozygote mice on a normal zinc diet showed a significant deficit in the percentage of time freezing in the cued fear conditioning test.
Description: Tbr1 het mice took a considerably longer time to realize that the reward had been changed to the other arm in the t maze
Exp Paradigm: The criterion to acquisition of learning was 80% correct responses on three consecutive days in appetitively motivated t maze
Description: Tbr1 het mice took a considerably longer time (no. of trials) to relearn that the food had been moved to the cinnamon scented bowl
Exp Paradigm: In the reveral learning phase the same bait (food) is mived to the bowl containing the cinnamon flavored sawdust. this was conducted one day after criterion level of six consecutive correct choices was achieved by mice in the previous acquisition phase. the reveral learning test was exactly the same as the first phase, starting with the four training trials to relearn that the food containing bowl had a different flavor
Description: Tbr1 heterozygote mice show a significantly reduced synaptic density of Shank3 in the lateral and basal amygdala. There are no significant differences in Shank2 synaptic expression between genotypes in either in lateral and basal amygdala.
Description: Following behavioral stimulation in the cta task, there was no upregulation of ntng1 and cdh8 protein in the amygdala in the tbr1 het mice unlike in the wt littermates
Exp Paradigm: Protein expression
Description: Following behavioral stimulation in the cta task, there was no induction of grin2b protein in the lateral and and reduced expression in the basal amygdala in the tbr1 het mice unlike in the wt littermates
Exp Paradigm: Protein expression
Description: Following behavioral stimulation in the cta task, there was no alteration of protein in the amygdala in the tbr1 het mice unlike in the wt littermates
Exp Paradigm: Protein expression
Description: Decreased inhibitory synapse numbers in the mpfc of tbr1+/-::rbp4- cre::tdtomato/+ (layer 5 neurons) and the somatosensory cortex of tbr1+/-::ntsr1-cre::tdtomato/+ (layer 6 neurons) at p56
Exp Paradigm: NA
Description: Mutants show decrease in calretinin positive interneurons in the external plexiform layer, mitral cell layer, and granular cell layer but not in the glomerular layer of the olfactory bulb compared with controls. mutants show enrichment in parvalbumin positive interneurons in the external plexiform layer of the olfactory bulb but a decrease in density in the entire olfactory bulb compared with controls, indicating a non-cell autonomous deficit in inhibitory interneurons. mutants show no change in the number of calbindin positive interneurons present only in the glomerular layer, compared with controls.
Exp Paradigm: Clr, clb, pv
Description: Decreased excitatory synapse numbers in the mpfc of tbr1+/-::rbp4- cre::tdtomato/+ (layer 5 neurons) and the somatosensory cortex of tbr1+/-::ntsr1-cre::tdtomato/+ (layer 6 neurons) at p56
Exp Paradigm: NA
Description: Mutants show no change in the volumes of the olfactory tubercle, piriform cortex, or perirhinal cortex compared with controls.
Exp Paradigm: Olfactory tubercle, piriform cortex, perirhinal cortex
Description: Mutants show no change in the volumes of the olfactory tubercle, piriform cortex, or perirhinal cortex compared with controls.
Exp Paradigm: NA
Description: Mutants show no change in tbr1, tbr2 or tbx21 expression patterns but show decrease in intensity and a decrease in triple positive excitatory projection mitral neurons in the olfactory bulb compared with controls.
Exp Paradigm: Olfactory bulb
Description: Mutants upon exposure to limonene show decrease in c-fos expressing activated neurons in the glomerular layer of the olfactory bulb but not in the external plexiform layer or the mitral cell layer of the olfactory bulb, compared with controls. mutants upon exposure to limonene show decrease in c-fos expressing neurons in the anterior piriform cortex, perirhinal cortex but not the olfactory tubercle compared with controls.
Exp Paradigm: C-fos expression was assayed after exposure to limonene; olfactory bulb
Description: Tbr1 het mice do not display preference for a new stranger mouse compared to the familiar stimulus (stranger) mouse in the three-chamber social approach test, unlike wild type controls. they spend the same amount of time with new and familiar stimulus mice in the second round of three-chamber social approach test.
Exp Paradigm: NA
Description: Tbr1 het mice show reduced social approach or preference towards a stranger stimulus mouse, compared to an empty cage in the three-chamber social approach test, similar to what was observed in previous reports
Exp Paradigm: NA
Description: Mutants spent less time sniffing the novel odor compared with controls resulting in a lower preference index for 2-heptanol in the 6th trial compared with controls, indicating a reduction in olfactory discrimination.
Exp Paradigm: Limonene (the familiar odorant) and 2-heptanol (a novel odorant) were simultaneously presented in the home cages of mice during trial 6 of the olfactory habituation-dishabituation test.
Description: Mutants show no expression of tbr1 full length transcript compared with controls, although a truncated transcript is expressed.
Exp Paradigm: NA
Description: Mutants show reduced corticothalamic innervation of layer 6 neurons in the anterior and anteromedial thalamus at p21 compared with controls. mutant layer 6 neurons have corticothalamic projections that enter the thalamus at p3 and 3 weeks similar to wildtype.
Exp Paradigm: NA
Description: Mutants show an abnormal pattern of sst+ cortical interneurons and their lamination in the sscx at p3 compared with controls.
Exp Paradigm: NA
Description: Decreased excitatory synapse numbers in the mpfc of tbr1+/-::rbp4- cre::tdtomato/+ (layer 5 neurons) and the somatosensory cortex of tbr1+/-::ntsr1-cre::tdtomato/+ (layer 6 neurons) at p56
Exp Paradigm: NA
Description: Mutants show two different subtypes of apical dendrites and ectopic growth of layer 6 apical dendrites into layer 1 compared with wildtype controls where apical dendrites of layer 6 neurons extend to layer 4 at p3, p21 and p60. changes in homozygotes emerge at p3 and persist into adulthood.
Exp Paradigm: NA
Description: Mutants show a decrease in sst positive cortical interneurons in layer 6, unchanged in layer 5, and an increase in layers 2/-4 of the somatosensory cortex compared with controls. mutants show no change in parvalbumin positive interneurons at p21 compared with controls.
Exp Paradigm: Pv
Description: Decreased inhibitory synapse numbers in the mpfc of tbr1-/-::rbp4- cre::tdtomato/+ (layer 5 neurons) and the somatosensory cortex of tbr1+/-::ntsr1-cre::tdtomato/+ (layer 6 neurons) at p56
Exp Paradigm: NA
Description: Mutants show increase in resonant frequency compared with controls in the deep layer neocortical pyramidal neurons. blocking hcn using hcn channel antagonist zd7288 reduced resonant frequency in mutants but not wildtype controls.
Exp Paradigm: NA
Description: Mutants have increased hyperpolarization activated cation currents compared with controls, in layer 6 pyramidal neurons of the sscx.
Exp Paradigm: NA
Description: Mutants show decrease in frequency of sipscs compared with cells from wild-type mice at p56 and p21 somatosensory cortex.
Exp Paradigm: NA
Description: Mutants show increase in aggressive encounters with a novel juvenile wild-type mouse of the same sex introduced to its home cage, compared with controls.
Exp Paradigm: NA
Description: Mutants show 178 differentially expressed genes compared with controls, including fezf2, bcl11b, foxp2, nr4a2, tle4 and wnt7b.
Exp Paradigm: NA
Description: Mutants show a decrease in sst positive cortical interneurons in layers 5 and 6 of the somatosensory cortex compared with controls. mutants show no change in parvalbumin positive interneurons at p21 compared with controls.
Exp Paradigm: Sst
Description: Mutants show two different subtypes of apical dendrites and ectopic growth of layer 6 apical dendrites into layer 1 compared with wildtype controls where apical dendrites of layer 6 neurons extend to layer 4 at p3, p21 and p60. changes in heterozygote mutants did not appear at p3 but emerged at 3 weeks and persisted on to adulthood.
Exp Paradigm: NA
Description: Mutants show an abnormal pattern of sst+ cortical interneurons and their lamination in the sscx at p3 compared with controls.
Exp Paradigm: NA
Description: Mutants show increase in resonant frequency compared with controls in the deep layer neocortical pyramidal neurons. blocking hcn using hcn channel antagonist zd7288 reduced resonant frequency in mutants but not wildtype controls.
Exp Paradigm: NA
Description: Mutants have increased hyperpolarization activated cation currents compared with controls, in layer 6 pyramidal neurons of the sscx.
Exp Paradigm: NA
Description: Mutants show increased locomotion during the first 6 h on day 1 during the light-off period, although total locomotion over 3 days did not change in light-off or light-on periods.
Exp Paradigm: NA
Description: Mutants show decrease in pv interneurons in the superficial cortical layers and increase in pv interneurons in the deep layers. mutants show no change in total sst-, pv-, and vip-positive gabaergic interneurons.
Exp Paradigm: Immunohistochemistry: sst-, pv-, and vip-positive gabaergic interneurons
Description: Mutant transcriptome was negatively enriched for gene sets associated with asd, synapse-related genes, pyramidal neurons, interneurons, and astrocytes suggesting underdevelopment of these cell types and suppressed neuroglial development and positively enriched for genes related with ribosomes, schizophrenia, and bipolar disorder.
Exp Paradigm: NA
Description: Mutant transcriptome was negatively enriched for gene sets associated with asd, non-neural cells such as astrocytes, microglia, ependymal cells, endothelial cells, and mural cells, and was positively enriched for gene sets associated with neurons generally and ca1 pyramidal neurons specifically, ribosome-related genes, and fmrp target gene set. [geo accession number: gse134526].
Exp Paradigm: NA
Description: Decreased vgat and gephyrin positive inhibitory synapse numbers on apical dendrites of layer 5 neurons (within layer 2-3) in the mpfc at p56 and p21
Exp Paradigm: NA
Description: Decreased vglut1 and psd95 positive excitatory synapse numbers on apical dendrites of layer 5 neurons (within layer 2-3) in the mpfc at p56 and p21
Exp Paradigm: NA
Description: Increased sag and rebound in response to steps of hyperpolarizing currents (ih) in rbp4-cre-tdtomato+ neurons of layer 5 in the mpfc; increased resonant frequency; blocking ih with hcn channel antagonist zd7288 decreased resonant frequency
Exp Paradigm: NA
Description: 320 differentially expressed genes clustered in go ontologies of axons, synapse, dendtrites, cell body and neurogenesis (geo: gse146298)
Exp Paradigm: NA
Description: Decreased vgat and gephyrin positive inhibitory synapse numbers on apical dendrites of layer 5 neurons (within layer 2-3) in the mpfc at p56 and p21
Exp Paradigm: NA
Description: Decreased vglut1 and psd95 positive excitatory synapse numbers on apical dendrites of layer 5 neurons (within layer 2-3) in the mpfc at p56 and p21
Exp Paradigm: NA
Description: Increased sag and rebound in response to steps of hyperpolarizing currents (ih) in rbp4-cre-tdtomato+ neurons of layer 5 in the mpfc; increased resonant frequency; blocking ih with hcn channel antagonist zd7288 decreased resonant frequency
Exp Paradigm: NA
Description: 470 differentially expressed genes clustered in go ontologies of axons, synapse, dendtrites, cell body and neurogenesis (geo: gse146298)
Exp Paradigm: NA
