التفاصيل البيبلوغرافية
| العنوان: |
Mutation of novel ethanol‐responsive lncRNAGm41261 impacts ethanol‐related behavioral responses in mice. |
| المؤلفون: |
Plasil, S. L., Farris, S. P., Blednov, Y., Mayfield, R. D., Mangieri, R. A., Nwokeji, U. J., Aziz, H. C., Lambeth, P. S., Harris, R. A., Homanics, G. E. |
| المصدر: |
Genes, Brain & Behavior; Feb2024, Vol. 23 Issue 1, p1-18, 18p |
| مصطلحات موضوعية: |
ETHANOL, ALCOHOLISM, NUCLEUS accumbens, LINCRNA, RNA analysis, PREFRONTAL cortex, GENE expression, DRINKING behavior |
| 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 GABAA receptor subunit composition in neurons of the nucleus accumbens shell. In C57BL6/J mice, TX2 within the cortex was cytoplasmic and largely present in Rbfox3+ neurons and IBA1+ microglia, but not in Olig2+ oligodendrocytes or in the majority of GFAP+ astrocytes. These data support the hypothesis that TX2 mutagenesis and dysregulation impacts ethanol drinking behavior and ethanol‐induced behavioral responses in mice, likely through alterations in the GABAergic system. [ABSTRACT FROM AUTHOR] |
|
Copyright of Genes, Brain & Behavior is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder