Myelination is a highly regulated process in the vertebrate central nervous system (CNS) whereby oligodendrocytes wrap axons with multiple layers of insulating myelin in order to allow rapid electrical conduction. Establishing the proper pattern of myelin in neural circuits requires communicative axo-glial interactions, however, the molecular interactions that occur between oligodendrocytes and axons during developmental myelination and myelin maintenance remain to be fully elucidated. Our previous work identified G protein-coupled receptor 62 (Gpr62), an uncharacterized orphan g-protein coupled receptor, as being selectively expressed by mature oligodendrocytes within the CNS, suggesting a potential role in myelination or axoglial interactions. However, no studies to date have assessed the functional requirement for Gpr62 in oligodendrocyte development or CNS myelination. To address this, we generated a knockout mouse strain lacking the Gpr62 gene. We assessed CNS myelination during both postnatal development and adulthood using immunohistochemistry, electron microscopy and western blot. In addition, we utilized AAV-mediated expression of a tagged Gpr62 in oligodendrocytes to determine the subcellular localization of the protein in vivo. We find that virally expressed Gpr62 protein is selectively expressed on the adaxonal myelin layer, suggestive of a potential role for Gpr62 in axo-myelinic signaling. Nevertheless, Gpr62 knockout mice display normal oligodendrocyte numbers and apparently normal myelination within the CNS during both postnatal development and adulthood. We conclude that in spite of being well-placed to mediate neuronal-oligodendrocyte communications, Gpr62 is overall dispensable for CNS myelination.

中文翻译：

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富含少突胶质细胞的孤儿 G 蛋白偶联受体 Gpr62 对于中枢神经系统髓鞘形成是可有可无的

髓鞘形成是脊椎动物中枢神经系统 (CNS) 中高度调节的过程，其中少突胶质细胞用多层绝缘髓鞘包裹轴突，以实现快速导电。在神经回路中建立正确的髓鞘模式需要交流的轴突-胶质相互作用，然而，在发育髓鞘形成和髓鞘维持过程中，少突胶质细胞和轴突之间发生的分子相互作用仍有待充分阐明。我们之前的工作确定了 G 蛋白偶联受体 62 (Gpr62)，一种未表征的孤儿 G 蛋白偶联受体，由 CNS 内的成熟少突胶质细胞选择性表达，表明在髓鞘形成或轴突相互作用中具有潜在作用。然而，迄今为止，还没有研究评估 Gpr62 在少突胶质细胞发育或 CNS 髓鞘形成中的功能要求。为了解决这个问题，我们产生了一个缺乏 Gpr62 基因的敲除小鼠品系。我们使用免疫组织化学、电子显微镜和蛋白质印迹评估了出生后发育和成年期的 CNS 髓鞘形成。此外，我们利用 AAV 介导的标记 Gpr62 在少突胶质细胞中的表达来确定蛋白质在体内的亚细胞定位。我们发现病毒表达的 Gpr62 蛋白在轴突髓鞘层上选择性表达，这表明 Gpr62 在轴突髓鞘信号传导中的潜在作用。然而，Gpr62 基因敲除小鼠在出生后发育和成年期的中枢神经系统内显示出正常的少突胶质细胞数量和明显正常的髓鞘形成。