Alterations in ciliary neurotrophic factor signaling in rapsyn deficient mice

Rapsyn is a key molecule involved in the formation of postsynaptic speciali zations at the neuromuscular junction, in its absence there are both pre- a nd post-synaptic deficits including failure to cluster acety]choline recept ors. Recently we have documented increases in both nerve-muscle branching a nd numbers of motoneurons, suggesting alterations in skeletal muscle derive d trophic support for motoneurons. The aim of the present study was to eval uate the contribution of target derived trophic factors to increases in mot oneuron branching and number, in rapsyn deficient mice that had their posts ynaptic specializations disrupted, We have used reverse transcription-polym erase chain reaction and Western blot to document the expression of known t rophic factors and their receptors in muscle, during the period of synapse formation in rapsyn deficient mouse embryos. We found that the mRNA levels for ciliary neurotrophic factor (CNTF) was decreased in the rapsyn deficien t muscles compared with litter mate controls although those for NGF, BDNF, NT-3 and TGF-beta2 did not differ. We found that both the mRNA and the prot ein expression for suppressor of cytokine signaling 3 (SOCS3) decreased alt hough janus kinase 2 (JAK2) did not change in the rapsyn deficient muscles compared with litter mate controls. These results suggest that failure to f orm postsynaptic specializations in rapsyn deficient mice has altered the C NTF cytokine signaling pathway within skeletal muscle, the target for moton eurons. This alteration may in part, account for the increased muscle nerve branching and motoneuron survival seen in rapsyn deficient mice. (C) 2001 Wiley-Liss, Inc.