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. Author manuscript; available in PMC: 2021 Aug 24.
Published in final edited form as: Cell Rep. 2021 Jul 20;36(3):109399. doi: 10.1016/j.celrep.2021.109399

Figure 1. Loss of VCP in forebrain neurons causes cortical brain atrophy.

Figure 1.

(A) VCP inactivation strategy.

(B) Agarose gel of cortical brain genomic DNA PCR amplification using primers A and F from (A), confirming LoxP recombination in VCPFL/WT or VCPFL/FL crossed to CaMKIIα-Cre mice (VCP cKO).

(C) Immunoblot for VCP and 14-3-3 (loading control) of cortical brain lysates from control (CamkCre) or VCP cKO mice at 1 and 2 months.

(D) VCP (red) immunofluorescence and DAPI nuclear (blue) fluorescence of coronal sections through the CA1 region of the hippocampus or cortex of 1-month-old VCP cKO mice and 2-month-old control mice (representative images of four control and six VCP cKO mice). Scale bars, 25 μm.

(E) Gross brain image of 2-month-old control (VCPFL/FL) or VCP cKO mice. Scale bar, 80 μm.

(F) Bar graph of brain weights from 2-month-old control or VCP cKO mice. Data represent mean ± SD (error bars) (n = 3 and 5 animals, respectively). *p < 0.05 by unpaired t test.

(G) Micrograph of 2-month-old control or VCP cKO coronal mouse brain sections stained with cresyl violet. Scale bars, 2.5 mm.

(H) Bar graph of cortical width from 2-month-old control of VCP cKO mice. ****p < 0.0001 by unpaired t test. Data represent mean ± SD (error bars) (n = 3 slices from four mice per group).

(I) Locomotor activity levels of VCP cKO mice (RM ANOVA interaction between genotype and age, F(1,52) = 103.6, p < 0.0001; ***p < 0.001 for each comparison within age). Data represent mean ± SEM (error bars) (n = 10 mice/group).

(J) Distance traveled to locate hidden platform (RM ANOVA) (F(4,80) = 3.187.6, p = 0.0176). Main effect of genotype p < 0.0001, with post hoc comparisons showing a shorter distance between genotypes by trial blocks 3 (*p < 0.05), 4 (***p < 0.001), and 5 (*p < 0.05). Data represent mean ± SEM (error bars) (n = 10 mice/group).

(K) Entries into the target zone during the probe trial compared to controls (**p < 0.01 by t test).

(L) Time searching the quadrant where platform is hidden (**p < 0.01 by t test). Data represent mean ± SEM (error bars) (n = 10 mice/group).