Striatum Gene Expression Correlates for HAND_BASELINE measured in BXD RI Females & Males obtained using GeneNetwork Striatum M430V2 (Apr05) RMA. The HAND_BASELINE measures Handling induced convulsion baseline under the domain Ethanol HIC. The correlates were thresholded at a p-value of less than 0.001.
Authors:
Philip VM, Duvvuru S, Gomero B, Ansah TA, Blaha CD, Cook MN, Hamre KM, Lariviere WR, Matthews DB, Mittleman G, Goldowitz D, Chesler EJ
QTL for nicotine sensitivity on Chr16 at D16Mit131 (8.72 Mbp , Build 37)
Description:
nicotine sensitivity spans 0.00 - 33.72 Mbp (NCBI Build 37) on Chr16. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL for METH responses for home cage activity on Chr16 at Comt (22.04 Mbp , Build 37)
Description:
METH responses for home cage activity spans 0.00 - 47.04 Mbp (NCBI Build 37) on Chr16. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
QTL associated with cocaine induced activation 12. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (76817838)
QTL associated with experimental allergic encephalomyelitis susceptibility11. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (70765248)
Authors:
Lindvall T, Nandakumar KS, Yousefi K, Holmdahl R, Andersson A
QTL associated with leishmaniasis resistance 18. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (86330968)
Authors:
Havelkov H, Badalov J, Svobodov M, Vojtkov J, Kurey I, Vladimirov V, Demant P, Lipoldov M
QTL associated with proteoglycan induced arthritis 10. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (85804079)
Authors:
Glant TT, Adarichev VA, Nesterovitch AB, Szanto S, Oswald JP, Jacobs JJ, Firneisz G, Zhang J, Finnegan A, Mikecz K
QTL associated with susceptibility to lung cancer 27. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (78812001)
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Alcohol use disorder (AUD) is a complex psychiatric disorder with strong genetic and environmental risk factors. We studied the molecular perturbations underlying risky drinking behavior by measuring transcriptome changes across the neurocircuitry of addiction in a genetic mouse model of binge drinking. Sixteen generations of selective breeding for high blood alcohol levels after a binge drinking session produced global changes in brain gene expression in alcohol-naïve High Drinking in the Dark (HDID-1) mice. Using gene expression profiles to generate circuit-level hypotheses, we developed a systems approach that integrated regulation of gene coexpression networks across multiple brain regions, neuron-specific transcriptional signatures, and knowledgebase analytics. Whole-cell, voltage-clamp recordings from nucleus accumbens shell neurons projecting to the ventral tegmental area showed differential ethanol-induced plasticity in HDID-1 and control mice and provided support for one of the hypotheses. There were similarities in gene networks between HDID-1 mouse brains and postmortem brains of human alcoholics, suggesting that some gene expression patterns associated with high alcohol consumption are conserved across species. This study demonstrated the value of gene networks for data integration across biological modalities and species to study mechanisms of disease.
Authors:
Laura B Ferguson, Lingling Zhang, Daniel Kircher, Shi Wang, R Dayne Mayfield, John C Crabbe, Richard A Morrisett, R Adron Harris, Igor Ponomarev
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_pvalue
Description:
To characterize transcriptional alterations that cocaine induces in these cells, we perform cell type-specific RNA-sequencing on FACS-isolated nuclei of somatostatin interneurons and identified 1100 DETs enriched for processes related to neural plasticity. To profile the entire (non poly-A selected) transcriptome of NAc somatostatin interneurons, we generated a transgenic reporter line (SST-TLG498 mice) to label the nuclei of these cells with a modified form of EGFP that is retained in the nuclear membrane (EGFP-F)22, enabling their isolation from NAc dissections using FACS. We succeeded in FACS-isolating nuclei suitable for RNA-sequencing from individual SST-TLG498 mice. We proceeded with differential expression analysis of the RNA-sequencing data to identify differentially expressed transcripts (DETs) in NAc somatostatin interneurons in response to repeated cocaine exposure: 778 transcripts were upregulated by cocaine and 322 were downregulated.
Authors:
Efrain A Ribeiro, Marine Salery, Joseph R Scarpa, Erin S Calipari, Peter J Hamilton, Stacy M Ku, Hope Kronman, Immanuel Purushothaman, Barbara Juarez, Mitra Heshmati, Marie Doyle, Casey Lardner, Dominicka Burek, Ana Strat, Stephen Pirpinias, Ezekiell Mouzon, Ming-Hu Han, Rachael L Neve, Rosemary C Bagot, Andrew Kasarskis, Ja Wook Koo, Eric J Nestler
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