Project description:Gene expression of Mef2c-het mice vs. WT littermates in hippocampus Total RNA isolated from hippocampus of P1 and P30 aged Mef2c-HET and WT mice using QIAGEN miRNeasy mini kit (QIAGEN; Cat #217004) were processed on an Illumina mouse Ref8 v2 beadchip microarrays following the manufacture’s protocol. Microarray data analysis was performed using R and Bioconductor packages. Raw expression data were log2 transformed and normalized by quantile normalization. Probes were considered robustly expressed if the detection P value was 0.01 for at least half of the samples in the data set.
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
Project description:Microdeletions of the MEF2C gene are linked to a syndromic form of autism termed MEF2C haploinsufficiency syndrome (MCHS). Here, we show that MCHS-associated missense mutations cluster in the conserved DNA binding domain and disrupt MEF2C DNA binding. DNA binding-deficient global Mef2c heterozygous mice (Mef2c-Het) display numerous MCHS-like behaviors, including autism-related behaviors, as well as deficits in cortical excitatory synaptic transmission. We find that hundreds of genes are dysregulated in Mef2c-Het cortex, including significant enrichments of autism risk and excitatory neuron genes. In addition, we observe an enrichment of upregulated microglial genes, but not due to neuroinflammation in the Mef2c-Het cortex. Importantly, conditional Mef2c heterozygosity in forebrain excitatory neurons reproduces a subset of the Mef2c-Het phenotypes, while conditional Mef2c heterozygosity in microglia reproduces social deficits and repetitive behavior. Together our findings suggest that MEF2C regulates typical brain development and function through multiple cell types, including excitatory neuronal and neuroimmune populations.
Project description:Comparison of gene expression profiles from Mus musculus brain (hippocampus) of animals kept in standard environment and enriched environment. The RNA-seq data comprise 4 groups: 2 age groups, each w/ and w/o enriched environment. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility.
Project description:Comparison of gene expression profiles from Mus musculus brain (hippocampus) of animals kept in standard environment and enriched environment. The RNA-seq data comprise 4 groups: 2 age groups, each w/ and w/o enriched environment. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:We collected whole genome testis expression data from hybrid zone mice. We integrated GWAS mapping of testis expression traits and low testis weight to gain insight into the genetic basis of hybrid male sterility. Gene expression was measured in whole testis from males aged 62-86 days. Samples include 190 first generation lab-bred male offspring of wild-caught mice from the Mus musculus musculus - M. m. domesticus hybrid zone.
Project description:Comparison of gene expression profiles from Mus musculus hippocampus after physical exercise (treadmill; endurance training over 4 weeks). The RNA-seq data comprise 4 groups: 2 age groups, each w/ and w/o physical exercise. Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)
Project description:To characterize the genetic basis of hybrid male sterility in detail, we used a systems genetics approach, integrating mapping of gene expression traits with sterility phenotypes and QTL. We measured genome-wide testis expression in 305 male F2s from a cross between wild-derived inbred strains of M. musculus musculus and M. m. domesticus. We identified several thousand cis- and trans-acting QTL contributing to expression variation (eQTL). Many trans eQTL cluster into eleven ‘hotspots,’ seven of which co-localize with QTL for sterility phenotypes identified in the cross. The number and clustering of trans eQTL - but not cis eQTL - were substantially lower when mapping was restricted to a ‘fertile’ subset of mice, providing evidence that trans eQTL hotspots are related to sterility. Functional annotation of transcripts with eQTL provides insights into the biological processes disrupted by sterility loci and guides prioritization of candidate genes. Using a conditional mapping approach, we identified eQTL dependent on interactions between loci, revealing a complex system of epistasis. Our results illuminate established patterns, including the role of the X chromosome in hybrid sterility.
