Expression of ciliary neurotrophic factor (CNTF) in charcot‐marie‐tooth type 1A (CMT1A) disease

Abstract

cDNA microarray experiments on sciatic nerves from 30‐day‐old PMP22 transgenic (PMP22tg) rats were performed to detect genes modulated in CMT1A. Among the downregulated genes, CNTF mRNA was significantly reduced, whereas other neurotrophic factors (BDNF, NT3, NGF) and cognate receptors (TRKA, TRKB, TRKC) were unchanged. We further studied CNTF expression in transgenic nerves using an ELISA technique. We observed significantly (p < 0.001) lower concentrations of the protein in sciatic nerves from homozygous (59 ± 7.8 pg/mg of proteins) and heterozygous (140.8 ± 17.56 pg/mg of proteins) PMP22tg nerves compared to normal controls (713.8 ± 168.7 pg/mg of proteins). Moreover, using real time PCR, we studied CNTF expression in human sural nerves from 2 CMT1A patients and in 3 control nerves. According to the animal results, CNTF mRNA expression was absent in CMT1A patients whereas it was detectable in control nerves (1.99 ± 0.9). Finally, we studied CNTF mRNA expression in aging PMP22tg rats; preliminary results show a further decrease of CNTF mRNA in heterozygous transgenic rats compared to normal age‐matched littermates. Our results suggest that reduced CNTF expression may account for the development of axonal atrophy in CMT1A.