Table 3.

Summary of studies examining the presence of TDP-43 CTF-25 and CTF-35 in transgenic mouse models of ALS/FTLD expressing wild-type or mutant forms of TDP-43.

Transgene	Promoter	Tissue analyzed	CTF-25	CTF-35	Other CTFs	Major findings	Reference
Wild-type hTDP-43	PrP	SC	+	+	-	Low levels of CTFs. Stronger labeling of FL-TDP-43 in nucleus and cytoplasm.	Stallings et al., 2010
		SC	+	+	-	Levels of FL-TDP-43 and CTFs was dose-dependent, with highest levels in homozygous mice.	Xu et al., 2010
	CaMKIIα	Brain	+	+	-	An antibody against total TDP-43 detected low levels of fragments in NT animals, and higher abundance in transgenic animals.	Cannon et al., 2012
		Brain	-	-	-	No CTFs detected despite progressive motor dysfunction.	Igaz et al., 2011
	Thy1.2	Brain	+	++	-	CTF-35 present from disease onset, CTF-25 increased by end stage.	Janssens et al., 2013
		Brain	+	++	-	Levels of soluble CTF-25 increased as disease progressed, whereas CTF-35 levels decreased. CTF-35 cytoplasmic, CTF-25 cytoplasmic and nuclear.	Wils et al., 2010
	Tardbp	Brain and SC	-	-	-	Very low or no CTF-35 and no CTF-25.	Swarup et al., 2011
Wild-type mTDP-43	CaMKIIα	Brain	+	++	-	Very low levels of fragments in transgenic animals aged to 6 months, but not animals aged to 2 months.	Tsai et al., 2010
hTDP-43A315T		Brain	-	+	15 and 20 kDa	CTFs less abundant than FL-TDP-43. Insoluble fragments highly phosphorylated at serine 409/410, while only some phosphorylation of the FL-TDP-43 was detected.	Ke et al., 2015
	PrP	Brain	+	+	-	CTF-25 detected in cytosol of mutant mice and NT controls. CTF-35 detected in nucleus and cytosol of transgenic animals only. CTFs less abundant than FL-TDP-43.	Medina et al., 2014
		SC	+	+	-	CTFs present in cytosol. FL-TDP-43 detected in nuclear and cytosolic fractions, and more abundant than CTFs.	Stallings et al., 2010
		Brain and SC	+	++	-	Low level detection of soluble CTFs prior to symptom onset and as disease progressed.	Wegorzewska et al., 2009
	Tardbp	Brain and SC	+	++	-	Higher levels of CTFs in mice aged to 10 months, but FL-TDP-43 more abundant overall.	Swarup et al., 2011
hTDP-43M337V	PrP	SC	+	+	-	Multiple faint bands between 25 and 35 kDa in cytosol, overall higher levels of FL-TDP-43 in nuclear and cytosolic fractions.	Stallings et al., 2010
		Brain	+	++	-	CTFs detected in both transgenic and NT mice by long exposure of immunoblot. FL-TDP-43 more abundant than CTFs.	Xu et al., 2011
	Thy1.2	Brain	+	++	-	CTF-35 present from disease onset, CTF-25 increased at end stage. Both lower than FL-TDP-43.	Janssens et al., 2013
	CaMKIIα	Cortex	+	++	-	Fragments were detected by antibodies against RRM2 of TDP-43 but not amino acids 3–12 or 404–414.	D’Alton et al., 2014
	TARDBP	Brain and SC	-	+	-	CTF-35 detected in cortex of transgenic and NT animals but not in SC.	Gordon et al., 2019
hTDP-43G348C	Tardbp	Brain and SC	+	+	-	Higher levels of CTFs in mice aged to 10 months, but CTFs overall less abundant than FL-TDP-43.	Swarup et al., 2011
ΔNLS	NEFH	SC	-	+	-	Very low levels of CTF-35 in both transgenic and control animals.	Walker et al., 2015a
	CaMKIIα	Brain	-	-	-	No detection of CTFs.	Igaz et al., 2011

“+” indicates that the fragment was present, “-” indicates that it was not detected, and “++” indicates higher abundance of one fragment relative to the other. CA3, cornu ammonis field 3; CTF, C-terminal fragment; CTF-25, TDP-43 CTF of 25 kDa; CTF-35, TDP-43 CTF of 35 kDa; Dox, doxycycline; FL-TDP-43, full-length TDP-43; h TDP-43, human TDP-43; NT, non-transgenic; RRM2, RNA recognition motif 2; SC, spinal cord.