Fig. 6.

Syt13 gene therapy prolongs the survival of SMA mice by preserving motor neurons and promoting NMJ integrity. a The righting performance of AAV9::Syt13 mice improved significantly compared to AAV9::null mice (P < 0.01, n = 10 mice/group, logistic regression). The histogram shows the percentage of mice that can perform the test. b Kaplan–Meier survival curves demonstrates significantly extended survival (by 6 days) in AAV9::Syt13 mice (n = 10) compared to AAV9::null mice (n = 10; χ² = 11.25, P = 0.0008). c, d Representative motor neurons (MNs) in the lumbar segment of the spinal cords of AAV9::null (c) and AAV9::Syt13 (d) mice (Nissl, blue). e, f Quantification of motor neurons (e) and their size (f) in the lumbar spinal cords of AAV9::Syt13 and AAV9::null mice (mean ± SEM). Motor neuron number and dimension significantly increases in the AAV9::Syt13 treatment group compared to the AAV9::null treated group (number: ***P < 0.0001, F(2,87) = 96.88, n = 30 slices counted/group, three mice/group; size: ***P < 0.0001, F(2,87) = 33.30, n = 30 slices counted/group, three mice/group; one-way ANOVA). g, h Analysis of α-bungarotoxin (BTX, red) and neurofilament M (NFM, green) in the intercostal muscles shows that AAV9::Syt13 treatment significantly increases the number of innervated NMJs in the SMA mice compared to AAV9::null treatment (i, ***P < 0.0001, χ²(2) = 75.34, n = 100 NMJs, six mice/group, contingency test). (l) Gross appearance of an AAV9::null mouse, which is not able to stand on four limbs, and a AAV9::Syt13 treated mouse at P10. Scale bar = 150 μm in c, d and 90 μm in g, h