دورية أكاديمية
Mutation of novel ethanol-responsive lncRNA Gm41261 impacts ethanol-related behavioral responses in mice.
| العنوان: | Mutation of novel ethanol-responsive lncRNA Gm41261 impacts ethanol-related behavioral responses in mice. |
|---|---|
| المؤلفون: | Plasil SL; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Farris SP; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA., Blednov Y; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA., Mayfield RD; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.; Department of Neuroscience, The University of Texas at Austin, Austin, Texas, USA., Mangieri RA; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.; Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA., Nwokeji UJ; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA., Aziz HC; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.; Division of Pharmacology and Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, Texas, USA., Lambeth PS; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA.; Department of Neuroscience, The University of Texas at Austin, Austin, Texas, USA., Harris RA; The Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, Texas, USA., Homanics GE; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. |
| المصدر: | Genes, brain, and behavior [Genes Brain Behav] 2024 Feb; Vol. 23 (1), pp. e12886. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Munksgaard Country of Publication: England NLM ID: 101129617 Publication Model: Print Cited Medium: Internet ISSN: 1601-183X (Electronic) Linking ISSN: 1601183X NLM ISO Abbreviation: Genes Brain Behav Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford : Munksgaard, c2002- |
| مواضيع طبية MeSH: | RNA, Long Noncoding*/genetics , Alcoholism*/genetics, Humans ; Female ; Mice ; Male ; Animals ; Ethanol/toxicity ; Alcohol Drinking/genetics ; Receptors, GABA-A/genetics ; Mutation ; Mice, Inbred C57BL |
| مستخلص: | Chronic alcohol exposure results in widespread dysregulation of gene expression that contributes to the pathogenesis of Alcohol Use Disorder (AUD). Long noncoding RNAs are key regulators of the transcriptome that we hypothesize coordinate alcohol-induced transcriptome dysregulation and contribute to AUD. Based on RNA-Sequencing data of human prefrontal cortex, basolateral amygdala and nucleus accumbens of AUD versus non-AUD brain, the human LINC01265 and its predicted murine homolog Gm41261 (i.e., TX2) were selected for functional interrogation. We tested the hypothesis that TX2 contributes to ethanol drinking and behavioral responses to ethanol. CRISPR/Cas9 mutagenesis was used to create a TX2 mutant mouse line in which 306 base-pairs were deleted from the locus. RNA analysis revealed that an abnormal TX2 transcript was produced at an unchanged level in mutant animals. Behaviorally, mutant mice had reduced ethanol, gaboxadol and zolpidem-induced loss of the righting response and reduced tolerance to ethanol in both sexes. In addition, a male-specific reduction in two-bottle choice every-other-day ethanol drinking was observed. Male TX2 mutants exhibited evidence of enhanced GABA release and altered GABA (© 2024 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.) |
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| معلومات مُعتمدة: | U01 AA013520 United States AA NIAAA NIH HHS; AA024836 United States AA NIAAA NIH HHS; AA020926 United States AA NIAAA NIH HHS; U01 AA020889 United States AA NIAAA NIH HHS; GM08424 United States NH NIH HHS; AA013520 United States AA NIAAA NIH HHS; AA020889 United States AA NIAAA NIH HHS; AA016651 United States AA NIAAA NIH HHS |
| فهرسة مساهمة: | Keywords: CRISPR/Cas9; alcohol use disorder; behavioral analysis; electrophysiology; gene-targeted; genetics; long noncoding RNA; molecular analysis; mouse; mutagenesis |
| المشرفين على المادة: | 3K9958V90M (Ethanol) 0 (RNA, Long Noncoding) 0 (Receptors, GABA-A) |
| تواريخ الأحداث: | Date Created: 20240219 Date Completed: 20240221 Latest Revision: 20240622 |
| رمز التحديث: | 20240623 |
| مُعرف محوري في PubMed: | PMC10876150 |
| DOI: | 10.1111/gbb.12886 |
| PMID: | 38373108 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1601-183X |
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| DOI: | 10.1111/gbb.12886 |