QTL for METH responses for body temperature on Chr1 at D1Ncvs75 (79.87 Mbp , Build 37)
Description:
METH responses for body temperature spans 54.87 - 104.87 Mbp (NCBI Build 37) on Chr1. 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 chronic alcohol withdrawal severity on Chr1 at D1Mit46 (83.89 Mbp , Build 37)
Description:
chronic alcohol withdrawal severity spans 58.89 - 108.89 Mbp (NCBI Build 37) on Chr1. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Bergeson SE, Kyle Warren R, Crabbe JC, Metten P, Gene Erwin V, Belknap JK
Genes with particular expression in the Lateral visual area, layer 6b. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Folium-tuber vermis (VII), molecular layer. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Folium-tuber vermis (VII). Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Folium-tuber vermis (VII), granular layer. Data represent fold expression difference in structure versus grey matter average expression.
Transcriptomic analysis of gene expression in the nucleus accumbens somatostatin interneurons of male 8�12-week-old Sst-Cre mice or Sst-Cre x TLG498 (SST-TLG498) mice following repeated cocaine intake. Expression was measured via RNA-seq. Values presented are p-values. Data taken from Supplementary Data 1. Data can be accessed at GEO with accession number: GSE116484.A7
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
Genes that are differentially expressed in adult male C57BL/6J mice given chronic cocaine vs. chronic saline. Tissue was collected from the ventral tegmental area (VTA) of the brain. Gene expression was evaluated via RNA-seq, and differential gene expression was determined via linear regression (LR).D13 Values presented are p-values. Data taken from Supplementary Table 1. Data available from GEO with accession number GSE155313."
Authors:
Rianne R Campbell, Siwei Chen, Joy H Beardwood, Alberto J López, Lilyana V Pham, Ashley M Keiser, Jessica E Childs, Dina P Matheos, Vivek Swarup, Pierre Baldi, Marcelo A Wood
Genes that are induced by THC in total lymph node (LN) cells in C57BL/6J mice. Gene expression was evaluated via RNA-seq. Values presented are "1" for effect presence. Data taken from Supplemental Data 1.
Authors:
Xiaoming Yang, Marpe Bam, Prakash S Nagarkatti, Mitzi Nagarkatti
Genes that are suppressed by THC in CD4 cells in C57BL/6J mice. Gene expression was evaluated via RNA-seq. Values presented are "1" for effect presence. Data taken from Supplemental Data 1.
Authors:
Xiaoming Yang, Marpe Bam, Prakash S Nagarkatti, Mitzi Nagarkatti
Alcohol transcriptome changes in mice microglia total homogenate log2FC
Description:
Microglia are fundamentally important immune cells within the central nervous system (CNS) that respond to environmental challenges to maintain normal physiological processes. Alterations in steady-state cellular function and over-activation of microglia can facilitate the initiation and progression of neuropathological conditions such as Alzheimer’s disease, Multiple Sclerosis, and Major Depressive Disorder. Alcohol consumption disrupts signaling pathways including both innate and adaptive immune responses that are necessary for CNS homeostasis. Coordinate expression of these genes is not ascertained from an admixture of CNS cell-types, underscoring the importance of examining isolated cellular populations to reveal systematic gene expression changes arising from mature microglia. Unbiased RNA-Seq profiling was used to identify gene expression changes in isolated prefrontal cortical microglia in response to recurring bouts of voluntary alcohol drinking behavior. The voluntary ethanol paradigm utilizes long-term consumption ethanol that results in escalated alcohol intake and altered cortical plasticity that is seen in humans. Gene coexpression analysis identified a coordinately regulated group of genes, unique to microglia, that collectively are associated with alcohol consumption. Genes within this group are involved in toll-like receptor signaling and transforming growth factor beta signaling. Network connectivity of this group identified Siglech as a putative hub gene and highlighted the potential importance of proteases in the microglial response to chronic ethanol. In conclusion, we identified a distinctive microglial gene expression signature for neuroimmune responses related to alcohol consumption that provides valuable insight into microglia-specific changes underlying the development of substance abuse, and possibly other CNS disorders.
Authors:
Gizelle M McCarthy, Sean P Farris, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains.
Authors:
Samuel J Harp, Mariangela Martini, Will Rosenow, Larry D Mesner, Hugh Johnson, Charles R Farber, Emilie F Rissman
Analysis using RNA-seq of FACS-purified oligodendrocytes revealed a large cohort of morphine-regulated genes. In addition, to investigate cell-type-specific opioid responses, we performed single-cell RNA sequencing (scRNA-seq) of the nucleus accumbens of mice following acute morphine treatment. Differential expression analysis uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes.
Authors:
Denis Avey, Sumithra Sankararaman, Aldrin K Y Yim, Ruteja Barve, Jeffrey Milbrandt, Robi D Mitra
Differential gene expression in nucleus accumbens somatostatin interneurons_cocaine_mice_logFC
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
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
Small intestine transcriptome changes in morphine treated mice. Eight-week-old, pathogen free, C57BL/6 male mice were used for this study (morphine n = 5, control n = 5). The animals were anesthetized using isoflurane (Pivetal®) and a 25mg slow-release morphine pellet or placebo pellet was implanted subcutaneously. Treatment lasted 16 hours. mRNA was purified from total RNA from using poly T-magnetic beads and strand specific library was constructed by using NEBNext Ultra RNA library prep kit. After quality control, the libraries were sequenced paired end by using Illumina sequencers (Illumina HiSeq 4000) for a read length of 150 base pairs. Clean reads were mapped to the mouse transcriptome using “STAR” software. The subsequent differential gene expression analysis was performed using DESeq2 R package (log2 (Fold change) > 1, P adj<0.05).
DEG female mouse forebrain 3-tri morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG female mouse forebrain PND1 morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG male mouse forebrain 3-tri morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG female mouse forebrain PND14 morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
DEG male mouse forebrain PND1 morphine vs saline_pvalue
Description:
To examine forebrain transcriptomic changes that might elucidate mechanisms of withdrawal, delayed development, and any long-term behavior changes, we generated transcriptomic signatures following our “3-trimester” exposure model (3-Tri). In addition, we also examined transcriptomes from animals that received opioids only during the gestational period (PND1) or only during the last trimester from PND 1–14 (PND 14). We sought to determine whether transcriptomic signatures vary based on the window of exposure, perhaps contributing to the discrepancies in the literature regarding acute and long-term outcomes. Brains were dissected from PND 1 pups 6 h after discovery. Brains were dissected from post-natal exposure only (PND 14) or 3-trimester exposure (3-tri) 6 h after the last morphine or saline injection. The number of animals per group was similar (N = 5–7 animals, male and female C57Bl/6NTac mice), and the quality controls, library construction and sequence parameters were also identical across all groups. Libraries were sequenced on a NovaSeq 6000 at a depth of 30 million total reads/sample using paired-end sequencing of 150 base pairs (PE150), to a depth of 30 million total reads/sample. Reads were then mapped to the mouse reference genome (Mus Musculus, GRCm38/mm10) using HISAT2 (version 2.2.1), and duplicated fragments were removed using Picard MarkDuplicates. Differential expression analysis between two conditions (e.g., Morphine and Saline) was performed in R (version 4.1.1) with DESeq2 (v1.32.0) package. Genes were assigned by the authors as differentially expressed if the (adjusted) (nominal) p-value < 0.05. All genes/scores are presented here.
Authors:
Amelia D Dunn, Shivon A Robinson, Chiso Nwokafor, Molly Estill, Julia Ferrante, Li Shen, Crystal O Lemchi, Jordi Creus-Muncunill, Angie Ramirez, Juliet Mengaziol, Julia K Brynildsen, Mark Leggas, Jamie Horn, Michelle E Ehrlich, Julie A Blendy
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