Fig. 5: miR106sp-mediated Mecp2 expression in the brain improves the neurobehavioral phenotype of RTT. | Nature Communications

Fig. 5: miR106sp-mediated Mecp2 expression in the brain improves the neurobehavioral phenotype of RTT.

From: Targeting microRNA-dependent control of X chromosome inactivation improves the Rett Syndrome phenotype

Fig. 5

A Immunoblot (Top) and quantitation (Bottom) of Mecp2 levels in the whole-brain lysates derived from the AAV9-miR106sp and AAV9-empty-injected Tsix-Mecp2 and control mice at ~16 weeks. n = 3. For AAV9-empty vs. AAV9-miR106sp, ***p = 0.00068; AAV9-miR106sp vs. Control, *p = 0.015; AAV9-empty vs. Control, *p = 0.036. B The lifespan of AAV9-miR106sp-injected mice (n = 15) compared with AAV9-empty-injected (n = 18), control (n = 18), Tsix-Mecp2 (n = 8) and Mecp2-/Y (n = 7) animals. The data was analyzed using the log-rank test. C Representative images of AAV9-empty-injected (n = 1) or AAV9-miR106sp-injected (n = 1) or control (n = 2) mice at ~12 weeks of age. D The percent changes of in vivo MRI brain volume (Left) and brain area (Right) in AAV9-empty-injected (n = 6) or AAV9-miR106sp-injected (n = 6) or control (n = 2) mice at ~6 weeks of age. Control animals were used as a reference for images and were excluded from the statistical analyses. For brain volume, AAV9-empty vs. AAV9-miR106sp, *p = 0.041. For brain area, AAV9-empty vs. AAV9-miR106sp, *p = 0.035. E, F Representative images (Top) and the quantitation (Bottom) of AAV9-empty-injected (n = 17) or AAV9-miR106sp-injected (n = 14) or control (n = 18) mice showing hind-limb clasping (E) and tail lesions (F). For the hind-limb clasp, AAV9-empty vs. AAV9-miR106sp, *p = 0.033. For the tail lesion, AAV9-empty vs. AAV9-miR106sp, *p = 0.024. G Latency to fall (mean + /- SEM) in rotarod test at 9, 12, and 16 weeks old AAV9-empty-injected (n = 13) or AAV9-miR106sp-injected (n = 12) or control (n = 12) mice. Data for the three consecutive days of evaluation is shown. The data was analyzed using a Welch one-way ANOVA with Dunnett’s post hoc multiple comparisons. H Averaged speed in the Barnes maze test for AAV9-empty-injected (n = 13) or AAV9-miR106sp-injected (n = 12) or control (n = 12) mice at 9, 12, and 16 weeks. Data for the five consecutive days of evaluation is shown. I Apneas (>0.5 sec.) measured by whole-body plethysmograph (mean + /- SEM) per 5 min as measured in AAV9-empty-injected or AAV9-miR106sp-injected or control mice at the indicated times (n = 6 animals per group). J Summary data (mean + /- SD) illustrating changes in short-term (SD1) and long-term (SD2) variabilities in the respiratory cycle period for AAV9-empty-injected or AAV9-miR106sp-injected or control mice at 9, 12, and 16 weeks (n = 6 animals per group). p-values are included in the Source data (G–J). Data is expressed as mean ± SD (A, D, G–J). Unpaired, two-sided t-test with no multiple adjustments (A, D, H–J).

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