Laboratoire de Biologie Moléculaire Eucaryote, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, Toulouse, France.
Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut National de la Santé et de la Recherche Médicale (INSERM), France Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université de Toulouse Université Paul Sabatier, Toulouse, France.
Elife. 2020 Oct 5;9:e60862. doi: 10.7554/eLife.60862.
has been proposed to promote the activity of serotonin (HTR2C) receptor via its ability to base pair with its pre-mRNA and regulate alternative RNA splicing and/or A-to-I RNA editing. Because genes are deleted in most patients with the Prader-Willi syndrome (PWS), diminished HTR2C receptor activity could contribute to the impaired emotional response and/or compulsive overeating characteristic of this disease. In order to test this appealing but never demonstrated hypothesis in vivo, we created a CRISPR/Cas9-mediated knockout mouse. Surprisingly, we uncovered only modest region-specific alterations in RNA editing profiles, while alternative RNA splicing was unchanged. These subtle changes, whose functional relevance remains uncertain, were not accompanied by any discernible defects in anxio-depressive-like phenotypes. Energy balance and eating behavior were also normal, even after exposure to high-fat diet. Our study raises questions concerning the physiological role of , notably its involvement in behavioural disturbance associated with PWS.
已经有人提出通过其与前体 mRNA 碱基配对的能力来促进血清素（HTR2C）受体的活性，从而调节选择性 RNA 剪接和/或 A-to-I RNA 编辑。由于大多数 Prader-Willi 综合征（PWS）患者的基因缺失，HTR2C 受体活性降低可能导致这种疾病特征性的情绪反应受损和/或强迫性暴饮暴食。为了在体内验证这一引人注目的但从未被证明的假说，我们创建了一种 CRISPR/Cas9 介导的基因敲除小鼠。令人惊讶的是，我们仅发现了 RNA 编辑谱中适度的区域特异性改变，而选择性 RNA 剪接没有改变。这些细微的变化，其功能相关性尚不确定，并没有伴随着焦虑抑郁样表型的任何明显缺陷。即使在暴露于高脂肪饮食后，能量平衡和饮食行为也正常。我们的研究提出了关于基因的生理作用的问题，特别是它与 PWS 相关的行为障碍的关系。
