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Altered social behavior in mice carrying a cortical Foxp2 deletion

ABSTRACT: Genetic disruptions of the forkhead box transcription factor FOXP2 in humans cause an autosomal-dominant speech and language disorder. While FOXP2 expression pattern are highly conserved, its role in specific brain areas for mammalian social behaviors remains largely unknown. Here we studied mice carrying a homozygous cortical Foxp2 deletion. The postnatal development and gross morphological architecture of mutant mice was indistinguishable from wildtype (WT) littermates. Unbiased behavioral profiling of adult mice revealed abnormalities in approach behavior towards conspecifics as well as in the reciprocal responses of WT interaction partners. Furthermore mutant mice showed alterations in acoustical parameters of ultrasonic vocalizations (USV), which also differed in function of the social context. Cell type-specific gene expression profiling of cortical pyramidal neurons revealed aberrant regulation of genes involved in social behavior. In particular Foxp2 mutants showed the downregulation of Mint2 (Apba2), a gene involved in approach behavior in mice and autism spectrum disorder in humans. Taken together these data demonstrate that cortical Foxp2 is required for normal social behaviors in mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE109596 | GEO | 2018/12/18

REPOSITORIES: GEO

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Sex-specific social behavior and amygdala proteomic deficits in Foxp2+/- mutant mice

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2021-07-07 | PXD026978 | Pride

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Altered social behavior in mice carrying a cortical Foxp2 deletion

Project description:Altered social behavior in mice carrying a cortical Foxp2 deletion

| PRJNA431442 | ENA

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2010-05-22 | E-GEOD-13588 | biostudies-arrayexpress

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Retinoic acid supplementation rescues the social deficits in Fmr1 knockout mice

Project description:Autism spectrum disorder (ASD) is a hereditary intellectual disability. Fragile X syndrome (FXS) is the leading cause of ASD and mainly results from the abnormal CGG amplification (>200 repeats) of the fragile X mental retardation 1 (Fmr1) gene. All-trans retinoic acid (RA) is involved in synaptic plasticity, neuronal differentiation and brain maturation. RA-mediated synaptic strength regulation was abolished in FXS patient-derived induced pluripotent stem (iPS) cells. Previous work on the ASD model with excessive UBE3A expression, of which the ASD-like behaviors caused by repression in RA signaling were successfully ameliorated by oral supplementation of RA. In this study, we used male Fmr1 knock-out (KO) mice to explore the effect of RA exerting on the behaviors. Our results indicated that RA supplementation can alleviate the defects in social novelty. We performed RNA sequencing to find out the differentially expressed genes (DEGs) in the Fmr1 KO group, of which the expression levels were restored to the similar level as those in the wild-type (WT) group after RA supplementation, such as Per1, Per2 and Foxp2. Besides, several DEGs associated with neuronal functions were also identified, like Arc, Ccn2, Foxp2, Xdh, Lepr, Serpina3n andTnfsf10. our findings that RA supplementation improved social novelty behavior in Fmr1 KO mice provided a potential therapeutic intervention method for FXS, which may further be used in other disease models with defective RA signaling.

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Humanized Foxp2 Accelerates Making Transitions From Declarative to Procedural Learning

Project description:Purpose: Foxp2 is the first and for now the only gene connected to speech and language in humans. Two aminoacid substitutions took place in this protein during recent human evolution, after our split from the last common ancestor with chimpanzees, and are most likely to have undergone positive selection in human lineage (Enard et al., 2002). Methods: Transgenic mice in which the wild-type (murine) version of Foxp2 was replaced with the one bearing two human-specific amino acid substitutions (i.e. "humanized" Foxp2) - Foxp2hum/hum, have been compared to their wild-type (WT) counterparts in terms of behavior, electrophysiology and striatal gene expression. The latter was analyzed through RNA-sequencing performed on pooled indexed libraries on three flow cells on Illumina GAIIx. The reads were mapped to mouse genome (mm9) by TopHat 1.4.1 and were counted using Bedtools. mRNA profiles were obtained with more than 20 million reads for every sample. Differential gene expression was analyzed with DESeq using multifactor model (Anders and Huber, 2010). Results: Wild-type and Foxp2hum/hum mice did not show any significant differences in expression at individual gene level, neither in dorsomedial nor in dorsolateral striatum. However, when genes were grouped into functional categories and analyzed accordingly, this revealed a significant downregulation of functional categories related to synaptic signalling and plasticity in dorsomedial striatum of Foxp2hum/hum mice. RNA-sequencing was performed on dorsomedial and dorsolateral striatum of wild-type and Foxp2hum/hum mice, on three flow cells Illumina GAIIx. The libraries from each sample were indexed and pooled together.

2014-09-24 | E-GEOD-60659 | biostudies-arrayexpress

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