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Positional candidate genes for VONFREYTHRESHOLDMEAN in BXD RI Females & Males on Chr9
Description:
Position candidates for VONFREYTHRESHOLDMEAN measured in BXD RI Females & Males. VONFREYTHRESHOLDMEAN measures Mechanical Sensitivity-Von Frey Threshold under the domain Pain. The QTL found was a Suggestive QTL and spans 114 Mb to 120 Mb.
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
cocaine related behavior 10 (Cocrb10) spans 93.149752 - 143.149752 Mbp (NCBI Build 37) on Chr 9. Obtained from MGI (http://www.informatics.jax.org) by searching for QTLs containing the keyword .
QTL for differences in cocaine responsiveness on Chr9 at D9M!t12 (94.40 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 69.40 - 119.40 Mbp (NCBI Build 37) on Chr9. 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 body temperature on Chr9 at D9Mit12 (103.09 Mbp , Build 37)
Description:
METH responses for body temperature spans 78.09 - 128.09 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
alcohol response 4 (a.k.a. high-dose ethanol actions) is associated with neurotensin immunoreactivity and sleep time after alcohol administration mapped to 55 cM on mouse Chromosome 9 near D9Mit12 (P=0.0006). This locus is named Alcrsp4 (alcohol response 4). Potential candidate genes found in this region are Chrna3 and Gnai2. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
Authors:
Erwin VG, Markel PD, Johnson TE, Gehle VM, Jones BC
QTL for differences in cocaine responsiveness on Chr9 at D9MIt2O (105.59 Mbp , Build 37)
Description:
differences in cocaine responsiveness spans 80.59 - 130.59 Mbp (NCBI Build 37) on Chr9. 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 cocaine seizure on Chr9 at D9Mit51 (111.26 Mbp , Build 37)
Description:
cocaine seizure spans 86.26 - 136.26 Mbp (NCBI Build 37) on Chr9. 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 Chr9 at D9Ncvs17 (114.61 Mbp , Build 37)
Description:
METH responses for home cage activity spans 89.61 - 139.61 Mbp (NCBI Build 37) on Chr9. 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 cocaine related behavior on Chr9 at D9Ncvs45 (118.15 Mbp , Build 37)
Description:
cocaine related behavior spans 93.15 - 143.15 Mbp (NCBI Build 37) on Chr9. 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 body temperature on Chr9 at Cck (118.82 Mbp , Build 37)
Description:
METH responses for body temperature spans 93.82 - 143.82 Mbp (NCBI Build 37) on Chr9. 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 body temperature on Chr9 at D9Byu6 (118.82 Mbp , Build 37)
Description:
METH responses for body temperature spans 93.82 - 143.82 Mbp (NCBI Build 37) on Chr9. 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 ethanol withdrawal on Chr9 at D9Byu6 (118.82 Mbp , Build 37)
Description:
ethanol withdrawal spans 93.82 - 143.82 Mbp (NCBI Build 37) on Chr9. 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 chewing on Chr9 at Tel9q (123.39 Mbp , Build 37)
Description:
METH responses for chewing spans 98.39 - 148.39 Mbp (NCBI Build 37) on Chr9. This interval was obtained by using an interval width of 25 Mbp around the peak marker (Build 37, MGI, http://informatics.jax.org).
BECs at LORR Recovery Chr# 9 rs13480854(7524005) with right flanking marker mCV23893269 (4062079) and left marker rs3663313 (123063108). This was mapped in 300 + (b6x129)F2 mice.
Genes with particular expression in the Spinal nucleus of the trigeminal, caudal part. Data represent fold expression difference in structure versus grey matter average expression.
Genes with particular expression in the Primary somatosensory area, trunk, layer 5. Data represent fold expression difference in structure versus grey matter average expression.
Genes associated with Danio rerio that interact with the MeSH term 'Atrazine' (D001280). Incorporates data from 6 publications curated by the Comparative Toxicogenomics Database (CTD). ODE Gene scores represent number of supporting publications per gene.
Chronic alcohol abuse alters the molecular structure and function of brain cells. Recent work suggests adaptations made by glial cells, such as astrocytes and microglia, regulate physiological and behavioral changes associated with addiction. Defining how alcohol dependence alters the transcriptome of different cell types is critical for developing the mechanistic hypotheses necessary for a nuanced understanding of cellular signaling in the alcohol-dependent brain. We performed RnA-sequencing on total homogenate and glial cell populations isolated from mouse prefrontal cortex (pfc) following chronic intermittent ethanol vapor exposure (cie). compared with total homogenate, we observed unique and robust gene expression changes in astrocytes and microglia in response to cie. Gene co-expression network analysis revealed biological pathways and hub genes associated with cie in astrocytes and microglia that may regulate alcohol-dependent phenotypes. Astrocyte identity and synaptic calcium signaling genes were enriched in alcohol-associated astrocyte networks, while tGf-β signaling and inflammatory response genes were disrupted by CIE treatment in microglia gene networks. Genes related to innate immune signaling, specifically interferon pathways, were consistently up-regulated across cie-exposed astrocytes, microglia, and total homogenate pfc tissue. This study illuminates the cell-specific effects of chronic alcohol exposure and provides novel molecular targets for studying alcohol dependence.
Authors:
Emma K Erickson, Yuri A Blednov, R Adron Harris, R Dayne Mayfield
Alcohol transcriptome changes in mice microglia total homogenate p-value
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
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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