This is a fascinating study on yet another TDP-43 transgenic mouse model
driven by the mouse Thy1.2 promoter. The most notable outcome to catch my attention was that TDP-43 intranuclear inclusions in motor neurons did not colocalize with survival motor neuron (SMN)-associated Gemini of coiled bodies (GEMs), but with a non-snRNP marker SC35, as well as with fused in sarcoma (FUS). FUS is another recently identified nuclear protein associated with ALS, and functional complexes of TDP-43 and FUS are beginning to be identified at the endogenous protein levels (Kim et al., 2010). Whether transiently increased TDP-43 pathologically sequesters FUS in ALS/FTLD remains to be shown. Also, whether such TDP-43 needs to be ubiquitinated or phosphorylated to be pathological remains to be studied.
The emerging consensus shows that although such inclusions might only be
infrequently or weakly ubiquitinated, these might contain some amounts
of phosphorylated TDP-43 as detected by phospho-specific p409/410 TDP-43
antibodies (Wils et al., 2010). On the other hand, the present study