Alcohol preference QTL 1 spans 26931283-76931283 (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). Phenotypically extreme HAP1/LAP1 animals (n=96) and HAP2/LAP2 animals (n=48) were screened for microsatellite markers in chromosomal regions previously reported to influence alcohol preference phenotypes. Linkage to alcohol preference, Alpq1, mapped to chromosome 9 near D9Mit4 (29 cM) in the HAP1/LAP1 set and near D9Mit90 (9 cM) in the HAP2/LAP2 set. The Alpq1 QTL interval is broad and may contain more than 1 underlying gene. Drd2 at 28 cM is a potential candidate for Alpq1.
Authors:
Bice PJ, Foroud T, Carr LG, Zhang L, Liu L, Grahame NJ, Lumeng L, Li TK, Belknap JK
Genes that are differentially expressed in adult male C57BL/6J mice with intravenous self-administration (ISVA) of cocaine vs. ISVA of 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). 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
Alcohol transcriptome changes in mice microglia 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
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