The VF rat with abnormal myelinogenesis has a mutation in Dopey1.
The VF rat with abnormal myelinogenesis has a mutation in Dopey1.
复制标题
髓鞘生成异常的 VF 大鼠的 Dopey1 发生突变。
DOI：
10.1002/glia.22698
复制
发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Kuwamura M.
中科院分区：
文献类型：
--
作者：
Tanaka M;Izawa T;Yamate J;Franklin RJM;Kuramoto T;Serikawa T;Kuwamura M.
空泡形成（VF）大鼠是一种常染色体隐性髓磷脂突变体，其特征为中枢神经系统（CNS）的全身性震颤、髓鞘形成不足和轴突周围空泡形成。在这里，我们报告了 VF 大鼠神经系统疾病最可能的致病基因，并探讨其在中枢神经系统髓磷脂的发育和维持中的作用。我们在大鼠第 8 号染色体上的 dopey 家族成员 1 (Dopey1) 中发现了一个无义突变。在 VF 大鼠的脊髓白质和灰质中，Dopey1 mRNA 的表达水平降低，并且 DOPEY1 蛋白均检测不到。双重免疫组化结果显示，野生型大鼠中DOPEY1主要表达于神经元和少突胶质细胞中，而VF大鼠中未检测到阳性细胞。我们还证明了 VF 大鼠髓鞘形成过程中髓鞘成分的 mRNA 和蛋白质水平均显着减少。此外，少突胶质细胞体内蛋白脂质蛋白和髓磷脂相关糖蛋白积累，表明Dopey1很可能参与髓磷脂成分的运输。我们的结果强调了 Dopey1 对于中枢神经系统髓磷脂的发育和维持的重要性。 GLIA 2014；62：1530–1542
The vacuole formation (VF) rat is an autosomal recessive myelin mutant characterized by generalized tremor, hypomyelination, and periaxonal vacuole formation of the central nervous system (CNS). Here, we report the most likely causative gene for neurological disease in the VF rat and pursue its roles in the development and maintenance of the CNS myelin. We identified a nonsense mutation in the dopey family member 1 (Dopey1) located on rat chromosome 8. Expression level ofDopey1mRNA was decreased and DOPEY1 protein was undetectable both in the white and gray matter of the spinal cords in the VF rats. Double immunohistochemistry demonstrated that DOPEY1 was mainly expressed in neurons and oligodendrocytes in the wild‐type rats, whereas no positive cells were detected in the VF rats. We also demonstrated a marked reduction in myelin components both at mRNA and protein levels during myelinogenesis in the VF rats. In addition, proteolipid protein and myelin‐associated glycoprotein accumulated in oligodendrocyte cell body, suggesting thatDopey1is likely to be involved in the traffic of myelin components. Our results highlighted the importance ofDopey1for the development and maintenance of the CNS myelin. GLIA 2014;62:1530–1542