Hackler Elizabeth A, Airey David C, Shannon Caitlin C, Sodhi Monsheel S, Sanders-Bush Elaine
Department of Pharmacology, Vanderbilt University Medical Center, 465 21st Avenue South, Medical Research Building III, Room 8140, USA..
Neurosci Res. 2006 May;55(1):96-104. doi: 10.1016/j.neures.2006.02.005. Epub 2006 Apr 3.
Post-transcriptional RNA editing of the G-protein coupled 5-hydroxytryptamine-2C (5-HT(2C)) receptor predicts an array of 24 receptor isoforms, some of which are characterized by reduced constitutive activity and potency to initiate intracellular signaling. The amygdala is integral to anxiety, fear, and related psychiatric diseases. Activation of 5-HT(2C) receptors within the amygdala is anxiogenic. Here, we describe the RNA editing profiles from amygdala of two inbred mouse strains (BALB/cJ and DBA/2J) known to be more anxious than a third (C57BL/6J). We confirmed the strain anxiety differences using light<-->dark exploration, and we discovered that BALB/cJ and DBA/2J are each characterized by a higher functioning RNA editing profile than C57BL/6J. BALB/cJ and DBA/2J exhibit a roughly two-fold reduction in C site editing, and a corresponding two-fold reduction in the edited isoform VSV. C57BL/6J is characterized by a relative decrease in the unedited highly functional isoform INI. We estimated the heritability of editing at the C site to be approximately 40%. By sequencing genomic DNA, we found complete conservation between C57BL/6J, BALB/cJ, DBA/2J and 37 other inbred strains for the RNA edited region of Htr2c, suggesting Htr2c DNA sequence does not influence variation in Htr2c RNA editing between inbred strains of mice. We did, however, discover that serotonin turnover is reduced in BALB/cJ and DBA/2J, consistent with emerging evidence that synaptic serotonin levels regulate RNA editing. These results encourage further study of the causes and consequences of 5-HT(2C) receptor RNA editing in the amygdala of mice.
G蛋白偶联的5-羟色胺2C（5-HT(2C)）受体的转录后RNA编辑可预测一系列24种受体亚型，其中一些亚型的特征是组成型活性降低以及启动细胞内信号传导的能力减弱。杏仁核对于焦虑、恐惧及相关精神疾病至关重要。杏仁核内5-HT(2C)受体的激活具有致焦虑作用。在此，我们描述了两种近交系小鼠（BALB/cJ和DBA/2J）杏仁核的RNA编辑谱，已知这两种小鼠比第三种小鼠（C57BL/6J）更易焦虑。我们通过明暗箱探索实验证实了品系间的焦虑差异，并且发现BALB/cJ和DBA/2J的RNA编辑谱功能均高于C57BL/6J。BALB/cJ和DBA/2J的C位点编辑大约减少了两倍，编辑亚型VSV也相应减少了两倍。C57BL/6J的特征是未编辑的高功能亚型INI相对减少。我们估计C位点编辑的遗传力约为40%。通过对基因组DNA进行测序，我们发现C57BL/6J、BALB/cJ、DBA/2J与其他37种近交系小鼠在Htr2c的RNA编辑区域完全保守，这表明Htr2c的DNA序列不影响小鼠近交系之间Htr2c RNA编辑的差异。然而，我们确实发现BALB/cJ和DBA/2J的血清素周转率降低，这与突触血清素水平调节RNA编辑的新证据一致。这些结果鼓励进一步研究小鼠杏仁核中5-HT(2C)受体RNA编辑的原因及后果。
