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. 2014 Jul 29;20(4):459–471. doi: 10.1038/mp.2014.69

Figure 5.

Figure 5

Peritoneal injection of PQBP1-AAV recovers the microcephaly and behaviors of nestin-Cre Pqbp1-cKO (conditional Pqbp1-knockout) mice. (a) Confirmation of the increase of Pqbp1 protein level in nestin-Cre Pqbp1-cKO mice after injection of PQBP1-AAV vector. Western blot analysis revealed a 2.5-fold increase. (b) The brain weight of nestin-Cre Pqbp1-cKO mice was recovered by PQBP1-AAV (*P<0.01 in Student's t-test). In multiple-group comparison with Tukey's test, the change was also confirmed (#P<0.05). (c) Macroscopic comparison of brain morphology between non-treated and AAV-injected male nestin-Cre Pqbp1-cKO mice at 2.5 months (10 weeks). (d) Comparison of coronal sections of the brain at the exactly same position of non-treated and AAV-injected male nestin-Cre Pqbp1-cKO mice at 2.5 months (10 weeks) revealed recovery of brain size by the PQBP1-AAV vector. (e) Staining for layer-specific markers, Cux1, Foxp1, and Tbr1, together with GAD67, shows the preservation of cortical layers in the rescue of nestin-Cre Pqbp1-cKO mice by the PQBP1-AAV vector at 2.5 months. (f) Quantitative analysis of the relative thickness of each layer to total thickness of the cortex. No difference was detected between AAV-injected and non-injected nestin-Cre Pqbp1-cKO mice. (g) The decline of nestin-Cre Pqbp1-cKO mice in the rotarod test was recovered at 3 months after birth by in utero gene therapy with the PQBP1-AAV vector. **P<0.01 in ANOVA with post hoc Tukey's test. (h) The decline of nestin-Cre Pqbp1-cKO mice in fear-conditioned memory was recovered at 3 months by in utero gene therapy with the PQBP1-AAV vector. **P<0.01 or *P<0.05 in ANOVA with post hoc Tukey's test.