Fig. 5: Defective spinogenesis and cognition in WWC1/2-deficient mice.

A, B Strategy for Wwc1/2^Syn-cKO mouse model and subsequent behavioral tests. Wwc1/2^fl/fl mice were crossed with Syn-Cre mice to generate Wwc1/2^Syn-cKO mice (A). Timeline of the indicated behavioral tests in Wwc1/2^fl/fl and Wwc1/2^Syn-cKO mice (B). C Representative images of dendritic branches of Golgi-stained prefrontal cortex pyramidal neurons (left) and hippocampal neurons (right) from Wwc1/2^fl/fl and Wwc1/2^Syn-cKO mice are shown. Scale bar, 2 μm. D Quantifications of dendritic spine density of the pyramidal neurons in the prefrontal cortex region (left, Wwc1/2^fl/fl, n = 22; Wwc1/2^Syn-cKO, n = 23) and hippocampal neurons in the dentate gyrus region (right, Wwc1/2^fl/fl, n = 21; Wwc1/2^Syn-cKO, n = 21) are shown. Data are shown as the mean ± SD; *p < 0.05, ***p < 0.001 between indicated groups. E Wwc1/2 deficiency is associated with impaired sequential alternations in Y maze test. Wwc1/2^fl/fl, n = 17; Wwc1/2^Syn-cKO, n = 15. Data are shown as the mean ± SD; **p < 0.01 between indicated groups. F Wwc1/2 deficiency is associated with impaired discrimination index in the novel object recognition test. Wwc1/2^fl/fl, n = 7; Wwc1/2^Syn-cKO, n = 7. Data are shown as the mean ± SD; *p < 0.05 between indicated groups. G–I Wwc1/2 deficiency is associated with impaired performance in the Morris water maze test. Quantifications of average time spent to reach the hidden platform during the 5 days training session (G), average time spent in target quadrant when the platform was absent (H), and representative path traces at day 5 (I) are shown. Wwc1/2^fl/fl, n = 11; Wwc1/2^Syn-cKO, n = 11. Data are shown as the mean ± SD; *p < 0.05 between indicated groups.