Fig. 1. Proteomic CSF screen in Vps35-depleted mice.
(A) Neuronal-selective Vps35 KO mice were generated by crossing mice expressing loxP-flanked Vps35 (Vps35fl/fl) with mice expressing Cre recombinase under the Camk2α promoter (upper left). Representative confocal images of 6-month-old mice brain sections stained for VPS35. Immunofluorescent images of the hippocampus show depletion of Vps35 in the neuron-selective KO mice (top right). Scale bars, 200 μm. Western blot analysis of hippocampal tissue from Vps35 cKO and control littermates (control) revealed for the retromer core proteins, VPS35, VPS26a, and VPS29. n = 4 animals per genotype. Data are shown as means ± SEM (bottom). (B) The CSF proteomic workflow is illustrated. Individual CSF samples (free of blood contamination) were pooled according to genotype, and the pooled samples were then analyzed by LC-MS/MS in technical duplicates. All data processing and statistical analysis were conducted as described in Materials and Methods. Significance is indicated as *P < 0.05, **P < 0.01, and ***P < 0.005.