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Overexpression of mutant HSP27 causes axonal neuropathy in mice

Title
Overexpression of mutant HSP27 causes axonal neuropathy in mice
Authors
Lee J.Jung S.-C.Joo J.Choi Y.-R.Moon H.W.Kwak G.Yeo H.K.Lee J.-S.Ahn H.-J.Jung N.Hwang S.Rheey J.Woo S.-Y.Kim J.Y.Hong Y.B.Choi B.-O.
Ewha Authors
우소연정성철
SCOPUS Author ID
우소연scopus; 정성철scopus
Issue Date
2015
Journal Title
Journal of Biomedical Science
ISSN
1021-7770JCR Link
Citation
vol. 22, no. 1
Keywords
AxonopathyCharcot-Marie-Tooth disease (CMT)Distal hereditary motor neuropathy (dHMN)Heat shock 27 kDa protein 1 (HSP27 or HSPB1)Magnetic resonance image (MRI)Mouse model
Publisher
BioMed Central Ltd.
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Background: Mutations in heat shock 27 kDa protein 1 (HSP27 or HSPB1) cause distal hereditary motor neuropathy (dHMN) or Charcot-Marie-Tooth disease type 2 F (CMT2F) according to unknown factors. Mutant HSP27 proteins affect axonal transport by reducing acetylated tubulin. Results: We generated a transgenic mouse model overexpressing HSP27-S135F mutant protein driven by Cytomegalovirus (CMV) immediate early promoter. The mouse phenotype was similar to dHMN patients in that they exhibit motor neuropathy. To determine the phenotypic aberration of transgenic mice, behavior test, magnetic resonance imaging (MRI), electrophysiological study, and pathology were performed. Rotarod test showed that founder mice exhibited lowered motor performance. MRI also revealed marked fatty infiltration in the anterior and posterior compartments at calf level. Electrophysiologically, compound muscle action potential (CMAP) but not motor nerve conduction velocity (MNCV) was reduced in the transgenic mice. Toluidine staining with semi-thin section of sciatic nerve showed the ratio of large myelinated axon fiber was reduced, which might cause reduced locomotion in the transgenic mice. Electron microscopy also revealed abundant aberrant myelination. Immunohistochemically, neuronal dysfunctions included elevated level of phosphorylated neurofilament and reduced level of acetylated tubulin in the sural nerve of transgenic mice. There was no additional phenotype besides motor neuronal defects. Conclusions: Overexpression of HSP27-S135F protein causes peripheral neuropathy. The mouse model can be applied to future development of therapeutic strategies for dHMN or CMT2F. © 2015 Lee et al.
DOI
10.1186/s12929-015-0154-y
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의학전문대학원 > 의학과 > Journal papers
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