A KO mouse model for the lncRNA Lhx1os produces motor neuron alterations and locomotor impairment

Here we describe a conserved motor neuron specific long non-coding RNA, Lhx1os, whose knock-out in mice produces motor impairment and post-natal reduction of mature motor neurons (MNs). The endoplasmic reticulum (ER)-stress response pathway resulted specifically altered with the downregulation of factors involved in the Unfolded Protein Response (UPR). Lhx1os was found to bind the ER-associated PDIA3 disulfide isomerase and to affect the expression of the same set of genes controlled by this protein, indicating that the two factors act in conjunction to modulate the UPR. Altogether, the observed phenotype and function of Lhx1os indicate its important role in the control of MN homeostasis and function. Expression profile of WT and Lh1os KO mice spinal cord tissues by high-throughput sequencing .本研究描述了一种保守的运动神经元特异性长链非编码RNA（long non-coding RNA）Lhx1os。在小鼠体内对该基因进行敲除后，可引发运动障碍，并导致出生后成熟运动神经元（MNs）的数量减少。内质网（ER）应激应答通路发生特异性改变，表现为未折叠蛋白反应（UPR）相关因子的表达下调。实验证实，Lhx1os可结合内质网关联的PDIA3二硫键异构酶，并影响该蛋白所调控的同一组基因的表达，提示二者协同作用以调控未折叠蛋白反应。综上，所观测到的Lhx1os的表型与功能表明，其在调控运动神经元稳态与功能方面发挥着重要作用。本数据集包含野生型（WT）与Lhx1os基因敲除（KO）小鼠脊髓组织的高通量测序表达谱。