Alterations in ciliary neurotrophic factor signaling in rapsyn deficient mice

Selena E. Bartlett, Glen B. Banks, Anna J. Reynolds, Mike J. Waters, Ian A. Hendry, Peter G. Noakes*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    10 Citations (Scopus)

    Abstract

    Rapsyn is a key molecule involved in the formation of postsynaptic specializations at the neuromuscular junction, in its absence there are both pre- and post-synaptic deficits including failure to cluster acetylcholine receptors. Recently we have documented increases in both nerve-muscle branching and numbers of motoneurons, suggesting alterations in skeletal muscle derived trophic support for motoneurons. The aim of the present study was to evaluate the contribution of target derived trophic factors to increases in motoneuron branching and number, in rapsyn deficient mice that had their postsynaptic specializations disrupted. We have used reverse transcription-polymerase chain reaction and Western blot to document the expression of known trophic 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 deficient muscles compared with litter mate controls although those for NGF, BDNF, NT-3 and TGF-β2 did not differ. We found that both the mRNA and the protein expression for suppressor of cytokine signaling 3 (SOCS3) decreased although janus kinase 2 (JAK2) did not change in the rapsyn deficient muscles compared with litter mate controls. These results suggest that failure to form postsynaptic specializations in rapsyn deficient mice has altered the CNTF cytokine signaling pathway within skeletal muscle, the target for motoneurons. This alteration may in part, account for the increased muscle nerve branching and motoneuron survival seen in rapsyn deficient mice.

    Original languageEnglish
    Pages (from-to)575-581
    Number of pages7
    JournalJournal of Neuroscience Research
    Volume64
    Issue number6
    DOIs
    Publication statusPublished - 15 Jun 2001

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