Camk2a cre

C57BL/6J WT, CAMK2A-Cre (The Jackson Laboratory, 005359), Vglut2-IRES-Cre (The Jackson Laboratory, 016963), and Vgat-IRES-Cre (The Jackson Laboratory, 016962) and non–Cre-expressing littermate mice (6–12 weeks, 20–25g) were used in this study (male C57BL/6J, both male and female transgenic strains). All mice were bred in a temperature- and humidity-controlled room on a 12-hour light/dark cycle with access to food and water ad libitum. The body weight and sexes of transgenic animals were assigned to different treatment groups randomly. All of the behavioral testing and electrophysiological recording experiments described herein were performed by experimenters who were blind to the treatments.

All the animal experiments were conducted according to relevant national and international guidelines, and approved by the Finnish Committee of Experimental Animal Research. The generation and validation of the loxP-mice is described elsewhere^{38 (link)}. Cre-expressing mouse lines: [Tg(Pgk1-cre)1Lni, Camk2a-cre, GFAP(73.12)-cre and mT/mG; The Jackson Laboratory, Stock No: 2178050, 005359, 012886, 007576 ME, USA] were crossed to lox-P mice. Cre-mediated excision of the floxed fragment produced a frame-shift mutation leading to a premature stop codon. For staging, the day of vaginal plug was counted as embryonic day 0.5 (E0.5). For PGK-cre-mice, embryos were collected at E7.5, at the time of which all genotypes were present. The astro/neuro-TwKO offspring were born in Mendelian ratios. The mice were regularly followed up by inspection for activity, and weighted. Beam walk test, conducted as previously published³⁹ . Briefly, the mice were trained to navigate the 1 m poles of two different diameters (1 and 1.5 cm) for two constitutive days and recorded on the third day. We also used the grip strength tester (BioSEB, USA) with each mouse recoded three times with 5 min intervals.

Mice were cared for according to animal protocols approved by Case Western Reserve University (CWRU) according to the National Institute of Health (NIH) guidelines. All mice were housed in standard conditions with food and water provided and a 12 h dark/light cycle. Vps35-floxed (Vps35^f/f) mice were generated, maintained, and genotyped as described previously [52 (link),53 (link)]. GFAP-Cre mice (stock 004600), as well as Emx1-Cre (stock 005628) and Camk2a-Cre (stock 027310) mice, were purchased from Jackson Laboratories. NeuroD6-Cre (also called Nex-Cre) mice were kindly provided by Klaus-Armin Nave. The Vps35^f/f mouse line was crossed with above Cre mouse lines to generate Vps35 homozygous mutant Vps35^Neurod6, Vps35^GFAP, Vps35^Emx1, and Vps35^Camk2a mice. All of the mouse lines indicated above were maintained in a C57BL/6 background for more than six generations. Mice were housed in 12/12 h light/dark cycle animal rooms. Both male and female mice were examined throughout all the experiments.

We used a previously generated transgenic mouse model of AD (human amyloid precursor protein {hAPP} KM670/671NL; human presenilin 1 {hPS1} L166P, further on referred to as APPPS1 mice), which develops Aβ pathology early in life accompanied by astro- and microgliosis and cognitive decline from 9 months on [24 (link)]. We crossbred these mice with EphA4^flox/flox (EphA4^tm1.1Bzh/J; stock number: 012916, The Jackson Laboratory) [25 (link)] and Camk2aCre (B6.Cg-Tg(Camk2a-Cre)T29-1Stl/J; stock number: 005359, The Jackson Laboratory) [26 (link)] mice to generate APPPS1 mice with a profound loss of EphA4 in the forebrain from the first postnatal weeks on. All mice were maintained in a C57/Bl6J background. All experiments were performed with mixed cohorts containing similar numbers of male and female mice.
Mice were housed in the “KU Leuven” animal facilities with a 12-h light-dark cycle at a temperature of 20 °C. Animals were given free access to standard rodent chow and water. All animal experiments were carried out in accordance with the National Institutes of Health guide for the care and use of laboratory animals (NIH publications No. 8023, revised 1978). Experiments were designed to minimize animal discomfort and were approved by the Ethical Committee for Animal Research of the University of Leuven, Belgium (P178/2013).