Overexpression of mutant HSP27 causes axonal neuropathy in mice

摘要: Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin. We generated a transgenic mouse model overexpressing HSP27-S135F mutant driven Cytomegalovirus (CMV) immediate early promoter. The phenotype was similar dHMN patients that they exhibit neuropathy. To determine the phenotypic aberration of mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed founder mice exhibited lowered performance. MRI also revealed marked fatty infiltration anterior posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not nerve conduction velocity (MNCV) reduced mice. Toluidine staining with semi-thin section sciatic ratio large myelinated axon fiber reduced, which might locomotion Electron microscopy abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level phosphorylated neurofilament tubulin sural There no additional besides defects. Overexpression causes peripheral can be applied future development therapeutic strategies for CMT2F.