The Role Of DAP12 In Peripheral Nervous System

Objective:DNAX activating protein of 12 k Da（DAP12）is a signal transduction adaptor molecule expressed in murine microglial cells,oligodendrocytes and so on in the central nervous system.DAP12-deficiency mice showed impaired differentiation of oligodendrocytes,synaptic degeneration and hypomyelinosis in the central nervous system.However,whether DAP12 is expressed in Schwann cells of peripheral nervous system（PNS）remains unknown.In this study,we are aim at identifying whether DAP12 is expressed in Schwann cells and investigate the effect of DAP12 deletion for the PNS.Methods:RT-PCR,Western blot,and immunofluorescence were performed to verify whether DAP12 is expressed in Schwann cells of PNS.Under the physiological and pathological conditions,changes of clinical phenotype,gait,electrophysiology,morphology and molecule in DAP12KO（DAP12-knockout,DAP12 KO）mice and WT（Wild type,WT）mice were compared to explore the role of DAP12 in the PNS.Results:The results of RT-PCR and Western blot revealed that DAP12 was expressed in sciatic nerve,and the immunofluorescence of sciatic nerve and Schwann cells showed DAP12 expressed in Schwann cells.Compared to WT mice,naso-anal length and body weight were increased significantly in DAP12 KO mice.Fasting blood glucose and hind-limb leg splaying were not found significant differences.There was no obvious changes of gait analysis and electrophysiological test in DAP12KO and WT at 8-week-old,but nerve function was impaired in DAP12 KO mice at 54-week-old.The mean intensity of MBP in DAP12 KO mice was lower than that in WT mice at 54-week-old.After sciatic nerve injury,the gait analysis showed motor function recover more quickly in DAP12 KO mice than WT mice.What’s more,the result of toluidine blue staining revealed the density of myelinated nerve fibers was significantly higher in DAP12 KO mice than WT mice.At the molecular level,there were higher mean fluorescence intensity of MBP,p75^NTR and MBP in DAP12 KO mice than WT mice.The proteomics profiles of sciatic nerve revealed that differentially expressed proteins（DEPs）were mainly associated with the process of cell growth at 8-week-old,while DEPs were enriched in immune response at 54-week-old and after sciatic nerve injury.Conclusion:In this study,we firstly demonstrated the expression of DAP12 in Schwann cells.Obvious obesity and increased weight exist in DAP12 KO mice.DAP12 deletion causes age-related functional impairment of peripheral nerve,but promotes the functional recovery after sciatic nerve crush injury.