Loss-of-function of the long non-coding RNA A830019P07Rik in mice does not affect insulin expression and secretion

Long non-coding RNAs (lncRNAs) contribute to diverse cellular functions and the dysregulation of their expression or function can contribute to diseases, including diabetes. The contributions of lncRNAs to ß-cell development, function and survival has been extensively studied in vitro. However, very little is currently known on the in vivo roles of lncRNAs in the regulation of glucose and insulin homeostasis. Here we investigated the impact of loss-of-function in mice of the lncRNA A830019P07Rik, hereafter P07Rik, which was previously reported to be associated with reduced plasma insulin levels. Compared with wild-type littermates, male and female P07Rik mutant mice did not show any defect in glycaemia and plasma insulin levels in both fed and fasted state. Furthermore, P07Rik mutant mice displayed similar glucose and insulin levels in response to an intra-peritoneal glucose tolerance test. Ex vivo, islets from mutant P07Rik released similar amount of insulin in response to increased glucose concentration as wildtype littermates. In contrast with previous reports, our characterization of P07Rik mouse mutants revealed that loss of function of this lncRNA does not affect glucose and insulin homeostasis in mice. Overall design: RNAseq of mouse islet in P07Rik KO and WT mice

长链非编码RNA（long non-coding RNAs，lncRNAs）参与多种细胞功能，其表达或功能失调可引发包括糖尿病在内的多种疾病。此前学界已在体外实验中广泛研究了lncRNAs对β细胞（β-cell）发育、功能及存活的调控作用。然而，目前对于lncRNAs在体内调控葡萄糖与胰岛素稳态中的作用却知之甚少。
本研究针对长链非编码RNA A830019P07Rik（下文简称P07Rik）的功能缺失型小鼠展开研究，此前有研究表明该lncRNA与血浆胰岛素水平降低存在关联。与野生型（WT）同窝仔鼠相比，无论处于饱腹还是禁食状态，P07Rik功能缺失型小鼠的血糖水平与血浆胰岛素水平均未出现异常。此外，腹腔葡萄糖耐量试验（intra-peritoneal glucose tolerance test）结果显示，P07Rik功能缺失型小鼠的血糖与胰岛素响应水平与野生型对照组无显著差异。离体实验中，P07Rik功能缺失型小鼠的胰岛在高葡萄糖浓度刺激下释放的胰岛素量与野生型同窝仔鼠无明显差异。与此前的研究报道相反，本研究对P07Rik功能缺失型小鼠的表型分析显示，该长链非编码RNA的功能缺失并不会影响小鼠的葡萄糖与胰岛素稳态。
实验整体设计：对P07Rik敲除（KO）与野生型（WT）小鼠的胰岛进行RNA测序（RNAseq）。