Figure 1. Df(16)A^+/− neurons show reduced density of spines and glutamatergic synapses.

(a) Schematic showing the human 22q11.2 region and the syntenic mouse region. The 1.5-Mb deletion found in patients is mediated by low copy repeat sequences LCR-A and LCR-B (red boxes). Dgcr2 and Hira, the two endpoints of the targeted deletion where loxP sites were inserted²³, are indicated by red arrowheads. The location of the human and mouse ZDHHC8 gene is indicated by an asterisk.

(b) Representative images of spines in Df(16)A^+/− neurons (DIV21) transfected with a EGFP, which fills and clearly defines dendritic protrusions. Scale bar, 1 µm.

(c) Reductions in the number of mushroom spines observed at DIV21 on Df(16)A^+/− neurons (estimated over 75 µm of dendritic length).

(d) Reductions in the width (left) and length (right) of mushroom spines on Df(16)A^+/− neurons. P < 0.05, K-S test.

(e) Properties of mEPSC recorded from autaptic individual pyramidal neurons grown on astrocytic microislands. Top left: the frequency at which events occurred was lower in Df(16)A^+/− neurons (n = 10) than in WT controls (n = 11). Top right: The average amplitude of mEPSCs was not different between genotypes. Bottom: Traces of recordings from a WT and a Df(16)A^+/− neuron. Scale bars, vertical: 20 pA, horizontal: 100 msec.

(f) Representative images of PSD95 puncta (green) and VGLUT1 puncta (red) and their co-localization in GFP (blue)-labeled hippocampal neurons at DIV21. Scale bar, 1 µm.

(g) Reduction in the number of PSD95 puncta in Df(16)A^+/− neurons at DIV21 and DIV9.

(h) Reduction in the number of VGLUT1 puncta in Df(16)A^+/− neurons at DIV21 and DIV12. Data are shown as mean ± S.E.M. * P < 0.05, *** P < 0.0001.