@entity248 -splicing of Tau exon 10 in XXXX type 1 is reproduced by overexpression of @entity67396 but not by @entity48973 silencing.

@entity1 @entity29726 @entity248 @entity6047 @entity13859 @entity67396 @entity179 @entity10731 @entity3918 @entity48973 @entity3668 @entity52551
Tau is the proteinaceous component of intraneuronal aggregates common to @entity179 called @entity13859 , including @entity3918 type 1. In @entity3918 type 1, the presence of @entity3668 aggregates is associated with a @entity248 -splicing of Tau. A toxic gain-of-function at the @entity10731 level is a major etiological factor responsible for the @entity248 -splicing of several transcripts in @entity3918 type 1. These are probably the consequence of a loss of @entity48973 ( @entity48973 ) function or gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) splicing function. Whether these two dysfunctions occur together or separately and whether all @entity248 -splicing events in @entity3918 type 1 brain result from one or both of these dysfunctions remains unknown. Here, we analyzed the splicing of Tau exons 2 and 10 in the brain of @entity3918 type 1 @entity1 . Two @entity3918 type 1 @entity1 showed a @entity248 -splicing of exon 10 whereas exon 2-inclusion was reduced in all @entity3918 type 1 @entity1 . In order to determine the potential factors responsible for exon 10 @entity248 -splicing, we studied the effect of the splicing factors @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ), @entity6047 and ETR3-like factor 2 ( @entity67396 ), and @entity6047 and ETR3-like factor 4 ( @entity52551 ) or a dominant-negative @entity6047 and ETR-3 like factor ( @entity29726 ) factor on Tau exon 10 splicing by ectopic expression or siRNA. Interestingly, the inclusion of Tau exon 10 is reduced by @entity6047 and ETR3-like factor 2 ( @entity67396 ) whereas it is insensitive to the loss-of-function of @entity48973 ( @entity48973 ), @entity6047 and ETR3-like factor 1 ( @entity6047 ) gain-of-function, or a dominant-negative of @entity6047 and ETR-3 like factor ( @entity29726 ) factor. Moreover, we observed an increased expression of @entity6047 and ETR3-like factor 2 ( @entity67396 ) only in the brain of @entity3918 type 1 @entity1 with a @entity248 -splicing of exon 10. Taken together, our results indicate the occurrence of a @entity248 -splicing event in @entity3918 type 1 that is induced neither by a loss of @entity48973 ( @entity48973 ) function nor by a gain of @entity6047 and ETR3-like factor 1 ( @entity6047 ) function but is rather associated to @entity6047 and ETR3-like factor 2 ( @entity67396 ) gain-of-function.
