Figure 5.

Morphological analysis of anterior lumbar roots and femoral motor nerves of 10-month-old R75W/Gjb1-null and N175D/Gjb1-null mice 4 months following post-onset intrathecal delivery of AAV9-Mpz.GJB1 or AAV9-Mpz.Egfp vectors

Representative images of semithin sections of R75W/Gjb1-null (A, B, E, and F) and N175D/Gjb1-null (C, D, G, and H) anterior motor lumbar spinal roots attached to the spinal cord, at low and higher magnification, as indicated. AAV9-Mpz.GJB1 injected mice show improved root myelination compared to mock-treated littermates with fewer demyelinated (∗) and remyelinated (r) fibers, as well as reduced numbers of foamy macrophages (arrows in E and G). Improved root pathology is confirmed by the morphometric analysis results showing decreased ratios of abnormally myelinated fibers and reduced numbers of macrophages per 1,000 fibers (I–L). Semithin sections of femoral motor nerves of R75W/Gjb1-null (M, N, Q, and R) and N175D/Gjb1-null (O, P, S, and T) at lower and higher magnification as indicated. The corresponding morphometric analysis results (U–X) from mock- and full-vector-treated mice confirm in AAV9-Mpz.GJB1 injected CMT1X mice of both genotypes improved myelination in femoral nerves compared to mock-treated littermates with fewer demyelinated and remyelinated fibers as well as reduction in the numbers of foamy macrophages. Values represent mean±SEM. Statistical analysis was performed using the Mann-Whitney test.