Expression profiling of sciatic nerve in a Charcot‐Marie‐Tooth disease type 1a mouse model

Abstract

Expression profiling was performed on sciatic nerve of normal mice and of transgenic mice overexpressing the peripheral myelin protein 22 kDa (PMP22). These mice represent a model for the hereditary peripheral neuropathy Charcot-Marie Tooth type 1A. Comparison of the profiles reveals that the proteasomal degradation pathway and various signaling mechanisms are up-regulated in the diseased nerve. The down-regulated processes represent cell shape and adhesion as well as cellular activity and metabolism. In addition, we found that the most significantly up-regulated differences could not be mapped on known transcripts and thus might represent not identified transcripts. Our data will be helpful to direct future research aimed at deciphering the molecular pathogenesis of the most prevalent hereditary peripheral neuropathy.

Animal models of inherited neuropathies

“…In contrast, transcripts related to cell proliferation were upregulated [96]. Both studies reported the downregulation of mRNA for ciliary neurotrophic factor (CNTF) [96,97]. Both studies reported the downregulation of mRNA for ciliary neurotrophic factor (CNTF) [96,97].…”

Peptide Mimetic of the S100A4 Protein Modulates Peripheral Nerve Regeneration and Attenuates the Progression of Neuropathy in Myelin Protein P0 Null Mice

“…Our data provide proof of principle that mimicking the S100A4 activity by H3 administration protects axons from secondary injury in the context of severe demyelination in a P 0 model. Further studies should be carried out to clarify whether this effect is limited to the particular context of the P 0 deficiency, or it can be extended to other demyelinating or axonal forms of CMT (53,54). At least two mechanisms may underlie the effects of H3 in the PNS.…”

Evaluation Tools and Animal Models of Peripheral Neuropathies

“…Recently, two different studies using cDNA micro-array of 30-day-old PMP22-overexpressing rats [56] or serial analysis of gene expression of adult PMP22-overexpressing mice [53] have shown similar up-regulation of genes related to cell proliferation and down-regulation of genes involved in cell cycle regulation, lipid and glucose metabolism, extracellular matrix formation and myelination. In addition, a very elegant study by GiamboniniBrugnoli et al [55] has attempted to delineate common as well as divergent mechanisms in animal models of hereditary neuropathies based on different PMP22 mutations.…”

“…Recently, gene expression profiles have been obtained from nerve samples of Charcot-Marie-Tooth disease (CMT) type 1A animal models [53,55,56] . In these studies, the genes identified may be responsible for causing the functional deficits and suggest pathways/processes that require further investigation as possible targets for therapeutic interventions.…”

“…These methods include differential display PCR [46] , subtractive hybridization [47] , expressed sequence tag analysis [48] , differential screening of a subtractive cDNA library [49] , cDNA micro-array analysis [50,51] and serial analysis of gene expression [52,53] . After identification of induced or repressed genes in a given condition, genes are classified into functional categories, drawing a general overview upon the signalling pathways modified in the pathological condition.…”