Table 1.

Summary results of characterized mouse models. The mouse breeding to obtain the experimental genotyped, the effect on axodendritic outgrowth, CREB signaling, and APP-CTF accumulation are summarized. Changes are indicated as strongly increase (↑↑), slightly increase (↑), slightly reduce (↓), no-change (-), or not determined (ND). Axodendritic components and associated CREB signaling alterations were evaluated in loss or partial loss of γ-secretase activity using γ-secretase inhibitor Compound E, PS1 KO, APPswe/PS1-ΔE9 (Tg85Dbo) and FAD-linked PSEN1-M146V knock-in (PS1 KI) mouse lines crossed to APP KO and DCC KO mice. Axonal as well as dendritic arborizations were increased in cortical neurons generated from PS1 KO, PS1 KI and Tg85Dbo mice. Augmentation of neurite extension correlates with the increase in CREB signaling and APP-CTF accumulation. Lack of APP expression in PS1 KI mice selectively alters axonal outgrowth that parallels a reduction in CREB signaling, as compared to their PS1 KI littermates. Lack of DCC expression in PS1 KI mice does not affect neurite outgrowth and CREB signaling, as compared to their PS1 KI littermates, therefore supporting the idea that APP is an essential substrate, but not DCC, in γ-secretase-mediated axodendritic plasticity.

DOI: http://dx.doi.org/10.7554/eLife.15645.019

Mouse models	Parental strains	Axonal outgrowth	Dendritic outgrowth	CREB signaling	APP-CTF
Compound E	WT	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$
PS1 KO	PS1+/- x PS1+/-	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$
PS1 KI/KI	PS1 KI/+ x PS1 KI/+	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow }$
Tg85Dbo	APPswe x PS1-ΔE9	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	ND	${\displaystyle \uparrow \uparrow }$
APP KO	APP+/- x APP+/-	${\displaystyle \downarrow }$	${\displaystyle -}$	${\displaystyle \downarrow }$	none
APP KO x PS1 KI	APP+/- x APP+/- PS1 KI/KI	${\displaystyle \downarrow }$	${\displaystyle -}$	${\displaystyle -}$	none
DCC KO	DCC+/- x DCC+/-	${\displaystyle -}$	${\displaystyle -}$	${\displaystyle -}$	ND
DCC KO x PS1 KI	DCC+/- x DCC+/- PS1 KI/KI	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	${\displaystyle \uparrow \uparrow }$	ND