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首页> 美国卫生研究院文献>ASN NEURO >Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination
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Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination

机译：靶向少突胶质细胞髓鞘碱性蛋白亚型导致少突胶质细胞成熟和髓鞘形成

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Recently, several in vitro studies have shown that the golli–myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells) and immature OLs (oligodendrocytes), and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing), is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination.
机译：最近，一些体外研究表明，golli-myelin碱性蛋白可调节OPC（少突胶质前体细胞）和未成熟OL（少突胶质细胞）中Ca 2 + 的同位稳态，并且这些蛋白的许多功能细胞受golli蛋白的细胞水平影响。为了确定体内糖蜜对OL发育和髓鞘形成的影响，生成了一种转基因小鼠，其中，糖蜜同工型J37特别在OL和OPC中过表达。名为JOE（过表达J37）的小鼠在出生与出生后第50天之间发生严重的髓鞘变性。在此期间，小鼠表现出严重的意图震颤，并在以后的年龄逐渐减弱。产后第50天后，超微结构研究以及Northern和Western印迹分析表明髓磷脂在大脑中积累，但从未达到正常水平。广泛的低髓鞘作用可能是几个因素造成的。体外和体内实验表明，golli过表达会导致OL成熟的显着延迟，并且在正常的髓鞘形成期间，大量无法髓鞘化的轴突前OL会大量积聚。带有细胞死亡和髓磷脂标志物的免疫组织化学研究表明，JOE OLs经历了延长且延长的细胞死亡期，直到出生后2个月才有效脱髓鞘。结果表明，OPC / OLs中的胶质水平升高会延迟髓鞘形成，从而导致OLs的大量细胞死亡，特别是在白质道中。该结果提供了体内证据，表明golli蛋白在OL的成熟和正常髓鞘形成的调节中起重要作用。

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