Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of mouse high and low exploratory genetically identical animals

ABSTRACT: Genetically identical inbred mice exhibit substantial stable individual variability in exploratory behavior. We used microarrays to look at gene expression differences in the hippocampus in female mice separated by stable differences in exploratory behavior Experiment Overall Design: Balb c/J offspring were briefly separated from mothers for 15 minutes each morning on postnatal days 1-14 (handled group) or left undisturbed. At 8 weeks of age mice were tested in the open-field and light-dark behavioral paradigms to verify a handling-induced behavioral phenotype. 2 weeks after behavioral testing, animals were sacrificed and the CA1 region was microdissected. CA1 regions were stored at -20C in RNA later. RNA was extracted from 8 samples (4 handled and 4 non-handled) using Trizol. RNA was extracted from second group of animals (7 handled and 10 non-handled) using Qiagen RNA/DNA columns. All total RNA samples were double round amplied and labeled using standard Affymetrix protocols and hybridized to Mouse 430_2.0 arrays in parallel.

ORGANISM(S): Mus musculus

SUBMITTER: mark alter

PROVIDER: E-GEOD-11680 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.

Alter Mark D MD Rubin Daniel B DB Ramsey Keri K Halpern Rebecca R Stephan Dietrich A DA Abbott L F LF Hen Rene R

PloS one 20081006 10

<h4>Background</h4>Despite sharing the same genes, identical twins demonstrate substantial variability in behavioral traits and in their risk for disease. Epigenetic factors-DNA and chromatin modifications that affect levels of gene expression without affecting the DNA sequence-are thought to be important in establishing this variability. Epigenetically-mediated differences in the levels of gene expression that are associated with individual variability traditionally are thought to occur only in ...[more]

PMID: 18836535

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Project description:Innate differences in human temperament strongly influence how individuals cope with stress and predispose for specific types of psychopathology. The present study examines the developing brain in an animal model of temperamental differences to understand how altered neurodevelopment may engender differences in emotional reactivity that are stable throughout the animal’s life. We utilize selectively-bred High Responder (bHR) and Low Responder (bLR) rats that exhibit dramatic emotional behavior differences, with bHRs exhibiting exaggerated novelty-exploration, aggression, impulsivity and drug self-administration, and bLRs showing marked behavioral inhibition, exaggerated anxiety- and depressive-like behavior. Using Affymetrix microarrays, we assessed bLR/bHR gene expression in the developing brain on postnatal days (P)7, 14, and 21, focusing on the hippocampus and nucleus accumbens, two regions related to emotionality and known to differ in adult bLR/bHR rats. We found dramatic bLR/bHR gene expression differences in the P7 and P14 hippocampus, with minimal differences in the nucleus accumbens. Some of the most profound differences involved genes critical for neurodevelopment and synaptogenesis. Stereological studies evaluated hippocampal structure in developing bHR/bLR pups, revealing enhanced hippocampal volume and cell proliferation in bLR animals. Finally, behavioral studies showed that the bHR/bLR behavioral phenotypes emerge very early in life, with exploratory differences apparent at P16 and anxiety differences present by P25. Together these data point to specific brain regions and critical periods when the bHR/bLR phenotypes begin to diverge, which may eventually allow us to test possible therapeutic interventions to normalize extreme phenotypes (e.g. the anxiety-prone nature of bLRs or drug addiction proclivity of bHRs). 2x2x3 factorial design with N=6 per group. Factors as follows: 1) Two selectively bred strains of rats (derived from an original Sprague Dawley population) termed High Responders (HR) and Low Responders (LR), 2) Two brain regions, Hippocampus (HPC) and Nucleus Accumbens (N.Acc), 3) Three developmental timepoints, specifically postnatal days 7 (P7), 14 (P14) and 21 (P21).

Dataset Information

Transcription profiling of mouse high and low exploratory genetically identical animals

Publications

Variation in the large-scale organization of gene expression levels in the hippocampus relates to stable epigenetic variability in behavior.

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