FMRP and myelin protein expression in oligodendrocytes
FMRP and myelin protein expression in oligodendrocytes
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DOI：
10.1016/j.mcn.2013.07.009
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发表时间：
2013-09-01
影响因子：
3.5
通讯作者：
Barbarese, Elisa
中科院分区：
文献类型：
--
作者：
Giampetruzzi, Anthony;Carson, John H.;Barbarese, Elisa
脆性X综合征（FXS）是由缺乏表达的脆性X智力低下蛋白（FMRP），Fmr 1基因的产物。在许多情况下，FXS与CNS髓鞘形成异常有关。尽管FMRP在少突胶质祖细胞和未成熟的少突胶质细胞（OLG）中表达，但之前的研究尚未在成熟的、产生髓鞘的OLG中检测到它。FMRP在体外抑制髓鞘碱性蛋白（MOP）RNA的翻译，并被认为可以防止未成熟OLG中MBP的过早表达。FXS中缺乏FMRP可能导致过早髓鞘形成和/或髓鞘异常。在这里，我们表明，FMRP表达在成熟的，MBP阳性的OLG的啮齿类动物和MBP阳性的人类OLG。我们证实，FMRP是MBP mRNA在体外的翻译阻遏物，但在浓度可能太高，在体内生理相关。我们发现MBP在培养的Fmr 1 KO OLG中的表达与野生型相似，并且MOP和其他髓鞘蛋白在Fmr 1 KO小鼠的脑匀浆中的表达在活跃髓鞘形成期间之前、期间和之后与野生型相似。这些结果表明，虽然FMRP在成熟的OLG中表达，但在啮齿动物中不再现由FXS中缺乏FMRP表达引起的髓鞘异常。(C)2013 Elsevier Inc. All rights reserved.
Fragile X syndrome (FXS) is caused by lack of expression of fragile X mental retardation protein (FMRP), the product of the Fmr1 gene. In many cases FXS is associated with abnormalities in CNS myelination. Although FMRP is expressed in oligodendrocyte progenitor cells and immature oligodendrocytes (OLGs) previous studies have not detected it in mature, myelin-producing OLGs. FMRP represses translation of myelin basic protein (MOP) RNA in vitro and is believed to prevent premature MBP expression in immature OLGs. Lack of FMRP in FXS could lead to premature myelination and/or myelin abnormalities. Here we show that FMRP is expressed in mature, MBP-positive OLGs of rodents and in MBP-positive human OLGs. We confirm that FMRP is a translational repressor of MBP mRNA in vitro, but at concentrations likely too high to be physiologically relevant in vivo. We find MBP expression in cultured Fmr1 KO OLGs to be similar to wild type, and expression of MOP and other myelin proteins in brain homogenates of the Fmr1 KO mouse to be similar to wild type before, during, and after the period of active myelination. These results suggest that while FMRP is expressed in mature OLGs, myelin abnormalities caused by lack of FMRP expression in FXS are not recapitulated in rodents. (C) 2013 Elsevier Inc. All rights reserved.