Figure 6: Lck^−/− mice exhibit characteristic pathology of the PNS.

(a) Sciatic nerves from 5-day WT and Lck^−/− mice were isolated and lysates were analysed for Oct-6 and Egr2 protein expression levels. Oct-6 expression levels are significantly lower in Lck^−/− sciatic nerves as compared with WT sciatic nerves (P=0.003, n=5, four nerves per sample, error bars represent ±s.d.). Conversely, no significant differences in Egr2 expression are seen. (b) Left panel shows an Lck^−/− SC forming compact myelin around a bundle that contains several small diameter axons suggesting an abnormal sorting process (arrow). Scale bar shows × 4,000 magnification. Right panel shows a P14 sciatic nerve of Lck^−/− mice with intimate interdigitations between the inner aspect of the SC and the axon (arrows). Scale bar denotes × 6,000 magnification. (c) Sciatic nerves from Lck^−/− mice show delay in myelination as compared with their WT littermates. Arrows (first panel bottom row) show SCs at P5 that have established a 1:1 relationship with large-diameter axons but have not initiated the myelination programme. Arrows in the remaining bottom panels denote several axons with thin myelin sheaths as compared with their WT littermates at 14 days, 4 months and 7 months. Arrowhead in the bottom right panel shows representative example of interleaved myelin folding in 7-month Lck^−/− mice. Scale bars denote × 4,000 magnification. (d) Quantification of the g-ratios versus axon diameters of myelinated axons between Lck^−/− and WT littermates at P5, P14, 4 and 7 months shows an abnormal distribution of g-ratios in Lck^−/− mice. (e) Quantification of the axon diameters and the g-ratios between sciatic nerves from Lck^−/− mice and their WT littermates in various time intervals (5days, 14 days, 4 months and 7 months). Axon diameters and g-ratios were quantified using sciatic nerves from two animals in each group and are plotted as average±s.d. Statistical significance was determined by two-tailed Student’s t-test.