TDP-43 is a developmentally regulated protein essential for early embryonic development.

Abstract

In the right-hand column (line 18), the sentence should read as follows: An example of the latter situation occurred with the ␣ 1-antitrypsin paralog (Serpina1b) knockout , which only partly removes elastase inhibitory activity in the circulation, suggesting that Serpina1a also contributes to elastase control in the mouse (44). Ref. 14 in the supplemental data should read as follows: Benarafa,

Changes in TDP-43 expression in development, aging, and in the neurofilament light protein knockout mouse

“…1). Bands at w43 and 70 kDa were strongly detected on the blot, corresponding to TDP-43 (Neumann et al, 2006;Sephton et al, 2010) and NF-L (Zhu et al, 1997), respectively (Fig. 1A).…”

“…TDP-43 is a developmentally regulated protein (Sephton et al, 2010); TDP-43 deficiency causes impaired neurite outgrowth (Fiesel et al, 2011) and ablating the gene results in early embryonic lethality in mice . Conversely, overexpression of the normal human TDP-43 gene, TARDBP, causes neurodegeneration in animal models such as mouse (Igaz et al, 2011;Stallings et al, 2010;Swarup et al, 2011;Xu et al, 2010), Drosophila (Li et al, 2010), and monkey (Uchida et al, 2012).…”

How do the RNA-binding proteins TDP-43 and FUS relate to amyotrophic lateral sclerosis and frontotemporal degeneration, and to each other?

“…Early studies using knockout or knockdown strategies in multiple organisms supported that loss of TDP-43 or FUS is severely detrimental, particularly during embryogenesis [60][61][62][63]. A study in frogs, for example, showed that FUS knockdown led to failed gastrulation, likely because of disrupted alternative splicing in several developmental genes [64].…”

Barriers to Novel Therapeutics in Amyotrophic Lateral Sclerosis

“…As mutations in the TARDBP gene most likely represent both loss-and gain-offunction mutations [96,97], new models have been established either with knockout mice [98][99][100] or with overexpression of TDP-43 using transgenic mice with different promoters or bacterial artificial chromosomes [101]. In addition, the knowledge about FUS and VCP mutations has led to new mouse models [102][103][104] and will add to the understanding of ALS.…”