Conditional knockout of TOG results in CNS hypomyelination.

The tumor overexpressed gene (TOG) protein is present in RNA granules that transport myelin basic protein (MBP) mRNA in oligodendrocyte processes to the myelin compartment. Its role was investigated by conditionally knocking it out (KO) in myelinating glia in vivo. TOG KO mice have severe motor deficits that are already apparent at the time of weaning.

CGG Repeats in the 5'UTR of FMR1 RNA Regulate Translation of Other RNAs Localized in the Same RNA Granules.

CGG repeats in the 5'UTR of Fragile X Mental Retardation 1 (FMR1) RNA mediate RNA localization and translation in granules. Large expansions of CGG repeats (> 200 repeats) in FMR1, referred to as full mutations, are associated with fragile X syndrome (FXS). Smaller expansions (55-200 repeats), referred to as premutations, are associated with fragile X tremor ataxia syndrome (FXTAS) and fragile X premature ovarian insufficiency (FXPOI).

Aberrant production of tenascin-C in globoid cell leukodystrophy alters psychosine-induced microglial functions.

Globoid cell leukodystrophy (GLD), or Krabbe disease, is a rare and often fatal demyelinating disease caused by mutations in the galactocerebrosidase (galc) gene that result in accumulation of galactosylsphingosine (psychosine). We recently reported that the extracellular matrix (ECM) protease, matrix metalloproteinase-3, is elevated in GLD and that it regulates psychosine-induced microglial activation. Here, we examined central nervous system ECM component expression in human GLD patients and in the twitcher mouse model of GLD using immunohistochemistry.

Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.

In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG) is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP) A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs) present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation.

FMRP and myelin protein expression in oligodendrocytes.

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.